Molecule Information

General Information of the Molecule (ID: Mol00111)

• Name: Multidrug resistance protein 1 (ABCB1) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: ABCB1
• Gene ID: 5243
• Location: chr7:87503017-87713323[-]
• Sequence:
  MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAII
  HGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSG
  IGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVS
  KINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFT
  DKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIG
  AAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARG
  AAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSG
  QTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLF
  ATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIA
  IARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAG
  FDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRS
  SLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAII
  NGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKA
  GEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNI
  ANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEA
  IENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFG
  AYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDS
  YSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVV
  QLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVV
  SQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLD
  EATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQL
  LAQKGIYFSMVSVQAGTKRQ
• Function: Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins. Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
• Uniprot ID: MDR1_HUMAN
• Ensembl ID: ENSG00000085563
• HGNC ID: HGNC:40

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 54 drug(s) in total

Ampicillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Staphylococcus infection [1]

• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Resistant Drug: Ampicillin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to ampicillin resistance in the staphylococcus infection.

Aspirin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Hypo-attenuated leaflet thickening [2]

• Resistant Disease: Hypo-attenuated leaflet thickening [ICD-11: BD10.2]
• Resistant Drug: Aspirin
• Molecule Alteration: SNP; rs1045642
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01).

Betamethasone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Betamethasone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Carbamazepine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Epilepsy [4]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Resistant Drug: Carbamazepine
• Molecule Alteration: SNP; rs1128503
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: ABCB1 polymorphisms were previously demonstrated to be associated with the metabolism and resistance of carbamazepine (CBZ) in epilepsy. ABCB1 rs1045642 and rs2032582 polymorphisms were associated with CBZ metabolism for epilepsy, and rs1128503 was related to carbamazepine resistance.

Carmustine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Malignant glioma [5]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Carmustine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: EDR assay
• Mechanism Description: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance.

Cefazolin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Staphylococcus infection [1]

• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Resistant Drug: Cefazolin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to cefazolin resistance in the staphylococcus infection.

Cefotetan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Staphylococcus infection [1]

• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Resistant Drug: Cefotetan
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to ampicillin resistance in the staphylococcus infection.

Chloroquine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Chloroquine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Staphylococcus infection [1]

• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to ciprofloxacin resistance in the staphylococcus infection.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Gastric cancer [6]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis and upregulating drug resistance-related genes.

Disease Class: Hepatocellular carcinoma [7]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• Experiment for Molecule Alteration: Western blot analysis; RNAi assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Knockdown of HOTAIR expression downregulated the MRP1 expression levels in the k562-imatinib cells and resulted in higher sensitivity to the imatinib treatment. In addition, the activation of PI3k/Akt was greatly attenuated when HOTAIR was knocked down in k562-imatinib cells.

Disease Class: Endometrial cancer [8]

• Resistant Disease: Endometrial cancer [ICD-11: 2C76.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• In Vitro Model: Ishikawa cells; Endometrium; Homo sapiens (Human); CVCL_2529
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
• Mechanism Description: HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.

Disease Class: Osteosarcoma [9]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: KHOS cells; Bone; Homo sapiens (Human); CVCL_2546
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay
• Mechanism Description: CircPVT1 knockdown reduces the expression of classical multidrug resistance related gene-ABCB1 in OS cells.

Disease Class: Lung cancer [10], [11]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: TGF-beta/Smad2/STAT3/STAT5 signaling pathway; Activation; hsa04350
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Vi-cell cell viability analyzer assay; MTS assay; Flow cytometry assay
• Mechanism Description: miR-21 achieves the drug resistance effect through three mechanisms: Increasing MDR1 and MPR1 expression levels, and enhancing drug efflux from the cells; increasing GSH, superoxide dismutase and GST-Pi expression levels and promoting drug inactivation; and inhibiting the PI3k signaling pathway and in turn inhibiting apoptotic signaling. And miR-10a had an important role in promoting drug resistance in tumors through enhancing drug efflux and inhibiting apoptosis via upregulation of MDR1, MRP1 and RhoE expression. In addition, miR-10a promoted the expression of TGF-beta as wells as regulated the activity of the Smad2/STAT3/STAT5 pathway and its downstream transcriptional factors of HIF and eIF4E, which may be the potential mechanism of drug resistance in A549 cells. Therefore, miR-10a may be an important drug target for improving cancer treatment; however, further studies are required to explore the clinical applications of miR-10a inhibitors.

Disease Class: Ovarian cancer [12]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CellTiter 96 aqueous one solution cell proliferation assay
• Mechanism Description: miR-130a and miR-374a mimics decreased the sensitivity of A2780 cells to cisplatin, reversely, their inhibitors could resensitize A2780/DDP cells. Furthermore, overexpression of miR-130a could increase the MDR1 mRNA and P-gp levels in A2780 and A2780/DDP cells, whereas knockdown of miR-130a could inhibit MDR1 gene expression and upregulate the PTEN protein expression. In a conclusion, the deregulation of miR-374a and miR-130a may be involved in the development and regulation of cisplatin resistance in ovarian cancer cells. This role of miR-130a may be achieved by regulating the MDR1 and PTEN gene expression.

Disease Class: Gastric cancer [13]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: mTOR/HIF-1alpha /P-gp/MRP1 signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance.PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1alpha. Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Disease Class: Malignant glioma [5]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: EDR assay
• Mechanism Description: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance.

Disease Class: Anaplastic astrocytoma [5]

• Resistant Disease: Anaplastic astrocytoma [ICD-11: 2A00.04]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: Oncotech EDR assay
• Mechanism Description: Cisplatin and etoposide are both substrates for membrane-bound efflux pumps, such as MRP and MDR1, which prevent their entry into the extracellular space of the central nervous system. The low levels of in vitro drug resistance noted for cisplatin and etoposide may be explained in part by the absence of such a barrier in our in vitro assay system.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cholangiocarcinoma [14]

• Sensitive Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: RBE cells; Liver; Homo sapiens (Human); CVCL_4896
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: miR199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1. miR199a-3p overexpression could reduce cisplatin induced MDR1 expression by decreasing the synthesis and increasing the degradation of MDR1, thus enhancing the effectiveness of cisplatin in cholangiocarcinoma.

Disease Class: Ovarian cancer [15]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: HO8910 cells; Ovary; Homo sapiens (Human); CVCL_6868
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: FTE187 cells; Ovary; Homo sapiens (Human); N.A.
• In Vitro Model: HG-SOC cells; Ovary; Homo sapiens (Human); N.A.
• In Vitro Model: HO8910PM cells; Ovary; Homo sapiens (Human); CVCL_0310
• Experiment for Molecule Alteration: Western blot analysis; Dual luciferase activity assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: microRNA-595 sensitizes ovarian cancer cells to cisplatin by targeting ABCB1. The expression level of ABCB1 was inversely correlated with miR595 in the ovarian cancer tissues, overexpression of ABCB1 decreased the miR595-overexpressing HO8910PM and SkOV-3 cell sensitivity to cisplatin.

Disease Class: Breast cancer [16]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-381 could overcome DDP resistance of breast cancer by directly targeting MDR1.

Disease Class: Lung cancer [17]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: Wnt signaling pathway; Inhibition; hsa04310
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Si-HOTAIR interference significantly increased the sensitivity of cells to DDP, the IC50 of cells was decreased from 131.85 to 44.34 M (P<0.05), the expression levels of MRP1 and MDR1 were significantly decreased, and the activation of Wnt signaling pathway was significantly inhibited.

Disease Class: Ovarian cancer [18]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Both A2780/DDP and A2780/Taxol cells expressed miR-186 at lower levels than A2780. miR-186 overexpression increased the sensitivity of ovarian cancer cell lines to paclitaxel and cisplatin compared with the negative control or mock cells, miR-186 transfection induced cell apoptosis while anti-miR-186 transfection reduced cell apoptosis, suggesting that miR-186 may inhibit the development of drug resistance in ovarian cancer cells. miR-186 overexpression may increase the sensitivity of ovarian cancer cells to paclitaxel by targeting ABCB1 and modulating GST-Pi.

Disease Class: Ovarian cancer [19]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-133b increases ovarian cancer cell sensitivity to cisplatin and paclitaxel by decreasing GST-Pi and MDR1 expression.

Disease Class: Esophageal squamous cell carcinoma [20], [21]

• Sensitive Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: ECA-109 cells; Esophagus; Homo sapiens (Human); CVCL_6898
• In Vitro Model: TE13 cells; Esophageal; Homo sapiens (Human); CVCL_4463
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax. And down-regulation of miR-27a significantly decreased expression of MDR1, but did not alter the expression of MRP, miR-27a could possibly mediate drug resistance, at least in part through regulation of MDR1 and apoptosis.

Disease Class: Gastric cancer [22]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Disease Class: Leukemia [23]

• Sensitive Disease: Leukemia [ICD-11: 2B33.6]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-138 was found up-regulated in the vincristine-induced multidrug resistance (MDR) leukemia cell line HL-60/VCR as compared with HL-60 cells. Up-regulation of miR-138 could reverse resistance of both P-glycoprotein-related and P-glycoprotein-non-related drugs on HL-60/VCR cells, and promote adriamycin-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of adriamycin.

Clopidogrel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Hypo-attenuated leaflet thickening [2]

• Resistant Disease: Hypo-attenuated leaflet thickening [ICD-11: BD10.2]
• Resistant Drug: Clopidogrel
• Molecule Alteration: SNP; rs1045642+rs2032562
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01).

Clozapine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Agranulocytosis [24]

• Resistant Disease: Agranulocytosis [ICD-11: 4B00.0]
• Resistant Drug: Clozapine
• Molecule Alteration: Missense mutation; 3435CC genotype
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: PCR
• Mechanism Description: It was shown that 3435CC genotype carriers require greater doses of clozapine to achieve same plasma concentrations compared with 3435CT and 3435TT carriers. Similarly, a study carried out in Switzerland reported that 3435TT carriers had higher clozapine plasma concentrations.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Agranulocytosis [24]

• Sensitive Disease: Agranulocytosis [ICD-11: 4B00.0]
• Sensitive Drug: Clozapine
• Molecule Alteration: Missense mutation; 3435TT genotype
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: PCR
• Mechanism Description: It was shown that 3435CC genotype carriers require greater doses of clozapine to achieve same plasma concentrations compared with 3435CT and 3435TT carriers. Similarly, a study carried out in Switzerland reported that 3435TT carriers had higher clozapine plasma concentrations.

Colchicine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Pituitary adenoma [25]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Colchicine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

Dacarbazine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Malignant glioma [5]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Dacarbazine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: EDR assay
• Mechanism Description: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance.

Daunorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Chronic myeloid leukemia [26]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Sensitive Drug: Daunorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: K562-R cells; Pleural effusion; Homo sapiens (Human); CVCL_5950
• In Vitro Model: NCI-H460/VBL cells; Bone marrow; Homo sapiens (Human); CVCL_0459
• In Vivo Model: SCID beige mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: In ABCB1-overexpressing cell lines, HG-829 significantly enhanced cytotoxicity to daunorubicin, paclitaxel, vinblastine, vincristine, and etoposide. Coadministration of HG-829 fully restored in vivo antitumor activity of daunorubicin in mice without added toxicity. Functional assays showed that HG-829 is not a Pgp substrate or competitive inhibitor of Pgp-mediated drug efflux but rather acts as a noncompetitive modulator of P-glycoprotein transport function.

Disease Class: Renal cell carcinoma [27]

• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Sensitive Drug: Daunorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Flp-In-293/Mock cells; Kidney; Homo sapiens (Human); CVCL_U421
• In Vitro Model: Flp-In-293/ABCB1 cells; Kidney; Homo sapiens (Human); CVCL_U421
• Experiment for Molecule Alteration: ATPase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.

Dexamethasone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Burkitt lymphoma [28]

• Resistant Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Resistant Drug: Dexamethasone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Dexamethasone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Burkitt lymphoma [28]

• Sensitive Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Sensitive Drug: Dexamethasone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glioma [29]

• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Disease Class: Colorectal carcinoma [29]

• Resistant Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Disease Class: Squamous cell carcinoma [29]

• Resistant Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• In Vitro Model: KB-V1 cells; Mouth; Homo sapiens (Human); CVCL_2089
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Disease Class: Cervical carcinoma [29]

• Resistant Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Disease Class: Anaplastic astrocytoma [5]

• Resistant Disease: Anaplastic astrocytoma [ICD-11: 2A00.04]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Protein kinase C signaling pathways; Inhibition; hsa04310
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: Oncotech EDR assay
• Mechanism Description: On the other hand, the frequency of LDR that we noted for paclitaxel (20%) and vincristine (20%) was similar to the clinical response rates for these compounds. These data suggest that although MDR1 expression by glial tumors may not be the dominant direct cellular process responsible for tumor resistance to natural products, other mechanisms are present that diminish their activity. The clinical mechanisms of natural product resistance may be a multifactorial function of endothelial expression of MDR1 at the blood-brain barrier in conjunction with glial tumor cell expression of alternative efflux pumps, such as MRP, altered tubulin with lower affinity binding sites, and/or protein kinase C signaling pathways that suppress apoptosis.

Disease Class: Malignant glioma [5]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: EDR assay
• Mechanism Description: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [30]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CellTiter AQueous One Solution Cell Proliferation Assay
• Mechanism Description: H19 LncRNA plays a leading role in breast cancer chemoresistance, mediated mainly through a H19-CUL4A-ABCB1/MDR1 pathway. H19 overexpression was contributed to cancer cell resistance to anthracyclines and paclitaxel.

Disease Class: Osteosarcoma [9]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: KHOS cells; Bone; Homo sapiens (Human); CVCL_2546
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay
• Mechanism Description: CircPVT1 knockdown reduces the expression of classical multidrug resistance related gene-ABCB1 in OS cells.

Disease Class: Breast cancer [31]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Activation; hsa01521
• Cell Pathway Regulation: p53 signaling pathway; Regulation; hsa04115
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MCF-7/ADR cells; Breast; Homo sapiens (Human); CVCL_1452
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Up-regulation of miR-200c with transfection of miR-200c mimics in breast cancer cells could enhance the chemosensitivity to epirubicin and reduce expression of multidrug resistance 1 mRNA and P-glycoprotein.

Disease Class: Leukemia [32]

• Resistant Disease: Leukemia [ICD-11: 2B33.6]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Western blotting analysis; Immunofluorescence analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The expression of miR-331-5p and miR-27a was inversely correlated with MDR1 expression. Transfection of exogenous miR-27a or miR-331-5p, or a combination of these two miRNAs, down-regulated MDR1 and increased sensitivity of the k562-resistant cancer cells to DOX.

Disease Class: Hepatocellular carcinoma [33]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Northern blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Antisense H19 oligonucleotides transfection induced a marked increase in the percentage of MDR1 promoter methylation and decrease in MDR1 expression in R-HepG2 cells. Thus, the H19 gene is believed to induce P-glycoprotein expression and MDR1-associated drug resistance at least in liver cancer cells through regulation of MDR1 promoter methylation.

Disease Class: Alveolar soft part sarcoma [34]

• Resistant Disease: Alveolar soft part sarcoma [ICD-11: 2F00.Y]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: KHOS cells; Bone; Homo sapiens (Human); CVCL_2546
• In Vitro Model: KHOSR2 cells; Bone; Homo sapiens (Human); CVCL_T432
• In Vitro Model: ES-X cells; N.A.; .; N.A.
• In Vitro Model: VAESBJ cells; Bone; Homo sapiens (Human); CVCL_1785
• In Vitro Model: ASPS-KY cells; Lung; Homo sapiens (Human); CVCL_S737
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: In comparison to Dox-sensitive cells (MCF-7 and KHOS), P-gp mRNA expression was upregulated in all Dox-resistant cells (VAESBJ, ES-X, ASPS-KY and KHOSR2 cells).

Disease Class: Burkitt lymphoma [28]

• Resistant Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Disease Class: Pituitary adenoma [25]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [35]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Inhibition; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Colony formation assay
• Mechanism Description: The protein levels of MDR1, MRP1 and ABCB1 were significantly decreased in DOXR-MCF-7 siR-HOTAIR1 cells compared with the siR-NC DOXR-MCF-7 cells and HOTAIR silencing reduces the sensitivity of drug resistance in drug-resistant MCF-7 cells.

Disease Class: Breast cancer [35]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Inhibition; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Colony formation assay
• Mechanism Description: The protein levels of MDR1, MRP1 and ABCB1 were significantly decreased in DOXR-MCF-7 siR-HOTAIR1 cells compared with the siR-NC DOXR-MCF-7 cells and HOTAIR silencing reduces the sensitivity of drug resistance in drug-resistant MCF-7 cells.

Disease Class: Hepatocellular carcinoma [36]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow Cytometric Analysis
• Mechanism Description: Transfection of miR122 mimics into cultured HepG2 cells induces cell-cycle arrest and sensitizes these cells to doxorubicin by modulating the expression of multidrug resistance genes, ABCB1 and ABCF2.

Disease Class: Osteosarcoma [37]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: HOS cells; Bone; Homo sapiens (Human); CVCL_0312
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1.

Disease Class: Solid tumour/cancer [38]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Disease Class: Chronic myeloid leukemia [39]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR9 regulates the multidrug resistance of chronic myelogenous leukemia by targeting ABCB1.

Disease Class: Gastric cancer [40], [41]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay assay
• Mechanism Description: MRUL depletion enhances the chemosensitivity of stomach cancer cells via inhibiting ABCB1 expression and increasing cell apoptosis. And The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Disease Class: Lung cancer [42]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Suppression of miR-155 in this cell line considerably reversed doxorubicin resistance, and doxorubicin-induced apoptosis and cell cycle arrest were recovered. Furthermore, reverse transcription-polymerase chain reaction and western blot analysis revealed that miR-155 suppression downregulated the expression of multidrug resistance protein 1, multidrug resistance-associated protein 1, breast cancer resistance protein, glutathione S-transferase-Pi, Survivin and B-cell lymphoma 2, and upregulated the expression of caspase-3 and caspase-8. In addition, it was found that miR-155 suppression inhibited the activation of AkT and extracellular signal-regulated kinase. The transcriptional activity of nuclear factor-kB and activator protein-1 was also downregulated.

Disease Class: Glioma [43]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: microRNA-127 silencing significantly affects cell growth and increases the sensitivity to adriamycin. microRNA-127 silencing arrests the cell cycle, potentiates adriamycin-induced apoptosis, and increases cellular Rh-123 uptake. microRNA-127 silencing down-regulates MDR1, MRP1, Runx2, Bcl-2, Survivin and ErbB4 expression while up-regulates p53 expression. microRNA-127 silencing inhibits AkT phosphorylation.

Disease Class: Hepatocellular carcinoma [44]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: The expression of a number drug resistance related proteins, including multidrug resistance 1, multi drug resistance associated protein 1, DNA excision repair protein ERCC 1, survivin and B cell lymphoma 2, was significantly downregulated by miR 503 overexpression.

Disease Class: Esophageal squamous cell carcinoma [20], [21]

• Sensitive Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: ECA-109 cells; Esophagus; Homo sapiens (Human); CVCL_6898
• In Vitro Model: TE13 cells; Esophageal; Homo sapiens (Human); CVCL_4463
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax. And down-regulation of miR-27a significantly decreased expression of MDR1, but did not alter the expression of MRP, miR-27a could possibly mediate drug resistance, at least in part through regulation of MDR1 and apoptosis.

Disease Class: Hepatocellular carcinoma [45]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: Skhep1 cells; Liver; Homo sapiens (Human); CVCL_0525
• In Vitro Model: HCC3 cells; Liver; Homo sapiens (Human); CVCL_0C57
• In Vitro Model: LM-6 cells; Liver; Homo sapiens (Human); CVCL_7680
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: miR-223 targeted ABCB1 3'UTR directly, and miR-223 down-regulated ABCB1 at both mRNA and protein levels. The over-expression of miR-223 increased the HCC cellsensitivity to anticancer drugs, and the inhibition of miR-223 had the opposite effect. Importantly, the over-expression or silencingof ABCB1 can rescue the cell response to the anticancer drugs mediated by miR-223 over-expression or inhibition.

Disease Class: Gastric cancer [22]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Disease Class: Leukemia [23]

• Sensitive Disease: Leukemia [ICD-11: 2B33.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-138 was found up-regulated in the vincristine-induced multidrug resistance (MDR) leukemia cell line HL-60/VCR as compared with HL-60 cells. Up-regulation of miR-138 could reverse resistance of both P-glycoprotein-related and P-glycoprotein-non-related drugs on HL-60/VCR cells, and promote adriamycin-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of adriamycin.

Disease Class: Breast cancer [46]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MCF-7/DOX cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blotting analysis; Immunofluorescence analysis
• Experiment for Drug Resistance: Celltiter-blue cell viability assay
• Mechanism Description: Expression of miR-451 is inversely correlated with mdr1 expression in breast cancer drug-resistant cells. Furthermore, the enforced increase of miR-451 levels in the MCF-7/DOX cells down-regulates expression of mdr1 and increases sensitivity of the MCF-7-resistant cancer cells to DOX

Disease Class: Liver cancer [47]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: High glucose upregulated the level of MDR-1, which can be expected the intracellular accumulation of anticancer drugs. Interestingly, reduced accumulation of doxorubicin was recorded in cells cultured in high glucose media. Curcumin-mediated inhibition of MDR-1 expression can be suggested as critical event leading to retention of anticancer drug in cellular interior.

Disease Class: Ovarian cancer [48]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Synergistic interaction between the MDR mechanisms include ABCT proteins (P-gp, BCRP, and MDR1) and metabolic enzymes of phase I of metabolism mainly CYP3A4, phase II of metabolism mainly GST was observed. In this study, FUC alone and in combination with DOX inhibited the enzyme activities of CYP3A4 and GST and down regulated their genes. We interpret this effect as a consequence of a down-regulation of pregnane X receptor (PXR) gene. FUC overcame MDR by significantly suppressing PXR mediated pathways that regulated the expression of CYP3A and ABCB1 genes in HepG-2 cells.

Disease Class: Breast cancer [48]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Synergistic interaction between the MDR mechanisms include ABCT proteins (P-gp, BCRP, and MDR1) and metabolic enzymes of phase I of metabolism mainly CYP3A4, phase II of metabolism mainly GST was observed. In this study, FUC alone and in combination with DOX inhibited the enzyme activities of CYP3A4 and GST and down regulated their genes. We interpret this effect as a consequence of a down-regulation of pregnane X receptor (PXR) gene. FUC overcame MDR by significantly suppressing PXR mediated pathways that regulated the expression of CYP3A and ABCB1 genes in HepG-2 cells.

Disease Class: Liver cancer [48]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Synergistic interaction between the MDR mechanisms include ABCT proteins (P-gp, BCRP, and MDR1) and metabolic enzymes of phase I of metabolism mainly CYP3A4, phase II of metabolism mainly GST was observed. In this study, FUC alone and in combination with DOX inhibited the enzyme activities of CYP3A4 and GST and down regulated their genes. We interpret this effect as a consequence of a down-regulation of pregnane X receptor (PXR) gene. FUC overcame MDR by significantly suppressing PXR mediated pathways that regulated the expression of CYP3A and ABCB1 genes in HepG-2 cells.

Disease Class: Burkitt lymphoma [28]

• Sensitive Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Disease Class: Embryonal rhabdomyosarcoma [49]

• Sensitive Disease: Embryonal rhabdomyosarcoma [ICD-11: 2B55.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MAST111 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: MAST139 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: NPE inhibited the activity of ABCB1. Upon 1h combination treatment of MAST139 cells with Vinblastine and 100 ug/ml of NPE , a 40% increase in doxorubicin retention was observed.

Disease Class: Alveolar rhabdomyosarcoma [49]

• Sensitive Disease: Alveolar rhabdomyosarcoma [ICD-11: 2B55.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: RH4 cells; Embryo; Homo sapiens (Human); CVCL_C357
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: NPE inhibited the activity of ABCB1. Upon 1h combination treatment of MAST139 cells with Vinblastine and 100 ug/ml of NPE , a 40% increase in doxorubicin retention was observed.

Disease Class: Renal cell carcinoma [27]

• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Flp-In-293/Mock cells; Kidney; Homo sapiens (Human); CVCL_U421
• In Vitro Model: Flp-In-293/ABCB1 cells; Kidney; Homo sapiens (Human); CVCL_U421
• Experiment for Molecule Alteration: ATPase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.

Efavirenz

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Human immunodeficiency virus infection [50]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Efavirenz
• Molecule Alteration: Missense mutation; c.C3435T
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Real-time PCR
• Mechanism Description: HIV-1 infected children with the MDR1-3435-C/T genotype had more rapid virologic responses to HAART at week 8 with higher plasma nelfinavir concentrations compared to those with the C/C genotype. Patients with the MDR1-3435-C/C genotype have been shown to have normal expression of P-gp on intestinal epithelial cells. In these patients, a substrate of P-gp is exported vigorously out of cells via P-gp after the substrate is absorbed through the intestinal epithelial cells. This leads to a lower intracellular concentration of substrate in the intestinal epithelial cells, followed by a lower concentration of substrate in plasma. In contrast, patients with the MDR1-3435-C/T or T/T genotype experience less elimination of the substrate through P-gp because of the lower expression of P-gp on intestinal epithelial.

Esomeprazole

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Non-small cell lung cancer [51]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Esomeprazole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Mechanism Description: Esomeprazole overcomes paclitaxel-resistance and enhances anticancer effects of paclitaxel by inducing autophagy in A549/Taxol cells. Esomeprazole could only result in a slight decrease in the expression of P-gp in A549/Taxol cells.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Hypertrophic scar [52]

• Resistant Disease: Hypertrophic scar [ICD-11: EE60.0]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Hypertrophic scar tissue isolates; .
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.

Disease Class: Ependymoma [53]

• Resistant Disease: Ependymoma [ICD-11: 2A00.05]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Disease Class: Anaplastic astrocytoma [5]

• Resistant Disease: Anaplastic astrocytoma [ICD-11: 2A00.04]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: Oncotech EDR assay
• Mechanism Description: Cisplatin and etoposide are both substrates for membrane-bound efflux pumps, such as MRP and MDR1, which prevent their entry into the extracellular space of the central nervous system. The low levels of in vitro drug resistance noted for cisplatin and etoposide may be explained in part by the absence of such a barrier in our in vitro assay system.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Ependymoma [53]

• Sensitive Disease: Ependymoma [ICD-11: 2A00.05]
• Sensitive Drug: Etoposide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Disease Class: Ependymoma [53]

• Sensitive Disease: Ependymoma [ICD-11: 2A00.05]
• Sensitive Drug: Etoposide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Esophageal squamous cell carcinoma [20], [21]

• Sensitive Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: ECA-109 cells; Esophagus; Homo sapiens (Human); CVCL_6898
• In Vitro Model: TE13 cells; Esophageal; Homo sapiens (Human); CVCL_4463
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: Down-regulation of miR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax. And down-regulation of miR-27a significantly decreased expression of MDR1, but did not alter the expression of MRP, miR-27a could possibly mediate drug resistance, at least in part through regulation of MDR1 and apoptosis.

Disease Class: Gastric cancer [22]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Disease Class: Leukemia [23]

• Sensitive Disease: Leukemia [ICD-11: 2B33.6]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-138 was found up-regulated in the vincristine-induced multidrug resistance (MDR) leukemia cell line HL-60/VCR as compared with HL-60 cells. Up-regulation of miR-138 could reverse resistance of both P-glycoprotein-related and P-glycoprotein-non-related drugs on HL-60/VCR cells, and promote adriamycin-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of adriamycin.

Guggulsterone

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [54]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Guggulsterone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MDA PCa 2b cells; Prostate; Homo sapiens (Human); CVCL_4748
• Experiment for Molecule Alteration: western blot; flow cytometry
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Guggulsterone is a novel and potent MDR reversal agent with the potential to be an adjunctive agent for tumor chemotherapy.

Hydrocortisone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Hydrocortisone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Disease Class: Chronic inflammatory lung disease [55]

• Resistant Disease: Chronic inflammatory lung disease [ICD-11: CA40.Z]
• Resistant Drug: Hydrocortisone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: For therapeutic drugs to be effective at reducing the proinflammatory/cytotoxic potential of steroid resistant lymphocytes, glucocorticoids enter cells by overcoming membrane drug efflux pump P-glycoprotein-1 (Pgp1) and binding to the glucocorticoid receptor (GCR) in the cytoplasm. GCR must be bound to the molecular chaperones heat shock proteins (Hsp)70 and Hsp90 to acquire a high-affinity steroid binding conformation, and trafficked to the nucleus where engagement of histone deacetylases (HDACs), particularly HDAC2, results in the reduction of pro-inflammatory gene activation.

Imatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Chronic myeloid leukemia [56]

• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Imatinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: UCA1 functions as a ceRNA of MDR1, UCA1 promotes IM resistance of CML cell through regulation of MDR1. Ectopic expression of MDR1 or silence of miR16 partially rescued this suppression induced by UCA1 knockdown.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Chronic myeloid leukemia [57]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Sensitive Drug: Imatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Annexin V-FITC/PI Apoptosis Detection assay
• Mechanism Description: Overexpression of MEG3 in imatinib-resistant k562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2.

Indomethacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Indomethacin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Irinotecan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Malignant glioma [5]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Irinotecan
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: EDR assay
• Mechanism Description: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance.

Ketorolac

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Acute myeloid leukemia [58]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: Ketorolac
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Efflux pump genes expression analysis
• Mechanism Description: Ketorolac-fluconazole in vitro combination would be a promising strategy for further clinical in vivo trials to overcome fluconazole resistance in AML patients on induction chemotherapy. To our knowledge, the current study is the first in vitro report on the use of ketorolac in reverting fluconazole resistance in C. albicans isolated from AML patients. Resistance of C. albicans to azole antifungals is associated with overexpression of efflux pump genes especially CDR1 and MDR1.

Levofloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Staphylococcus infection [1]

• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Resistant Drug: Levofloxacin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to levofloxacin resistance in the staphylococcus infection.

Loperamide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Diarrhea [59]

• Sensitive Disease: Diarrhea [ICD-11: DA90.0]
• Sensitive Drug: Loperamide
• Molecule Alteration: Missense mutation; Haplotype G2677/T3435
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Experiment for Drug Resistance: Assessment of central opioid effects assay
• Mechanism Description: The results support a functional importance of the ABCB1 genetic variants for the pharmacokinetics of loperamide. Highest loperamide plasma concentrations were seen in carriers of haplotype G2677.

Melphalan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Burkitt lymphoma [28]

• Resistant Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Resistant Drug: Melphalan
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Burkitt lymphoma [28]

• Sensitive Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Sensitive Drug: Melphalan
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Methotrexate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Osteosarcoma [60]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Resistant Drug: Methotrexate
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell senescence; Inhibition; hsa04218
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: LUCAT1/miR200c/ABCB1 pathway; Regulation; hsa05206
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HOS cells; Bone; Homo sapiens (Human); CVCL_0312
• In Vitro Model: HFOB cells; Bone; Homo sapiens (Human); CVCL_3708
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Transwell invasion assay
• Mechanism Description: LncRNA LUCAT1 and ABCB1 protein were both up-regulated in MG63/MTX and HOS/MTX cells when treated with methotrexate. ABCB1, acting as a vital protein of drug resistance, participated in the multiple drug resistance occurrence.

Disease Class: Ependymoma [53]

• Resistant Disease: Ependymoma [ICD-11: 2A00.05]
• Resistant Drug: Methotrexate
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Disease Class: Psoriasis [61]

• Resistant Disease: Psoriasis [ICD-11: EA90.0]
• Resistant Drug: Methotrexate
• Molecule Alteration: SNP; rs1045642 TT
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The SNP of ABCB1 led to methotrexate resistance in the resistance.

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Methotrexate
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Disease Class: Systemic lupos erythematosus [62]

• Resistant Disease: Systemic lupos erythematosus [ICD-11: 4A40.2]
• Resistant Drug: Methotrexate
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Up-regulation of P-glycoprotein led to methotrexate resistance in the staphylococcus infection.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Ependymoma [53]

• Sensitive Disease: Ependymoma [ICD-11: 2A00.05]
• Sensitive Drug: Methotrexate
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Disease Class: Ependymoma [53]

• Sensitive Disease: Ependymoma [ICD-11: 2A00.05]
• Sensitive Drug: Methotrexate
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Methylprednisolone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Methylprednisolone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Miltefosine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Leishmaniasis [63]

• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Resistant Drug: Miltefosine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: In addition, the overexpression of ABC transporters ABCB4(MDR1), ABCG4, and ABCG6 has also been described to be associated with an increased resistance to several alkyl-lysophospholipids analogues, including MIL in Leishmania, due to a reduced intracellular accumulation because of increased efflux of the drug across the plasma membrane.

Mitoxantrone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Keloid [64]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Resistant Drug: Mitoxantrone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

Disease Class: Keloid [64]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Resistant Drug: Mitoxantrone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

Nitrofurantoin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Staphylococcus infection [1]

• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Resistant Drug: Nitrofurantoin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to nitrofurantoin resistance in the staphylococcus infection.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Gastric cancer [65]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: miR125a/hexokinase 2 pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell assay
• Mechanism Description: BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361.

Disease Class: Gastric cancer [65]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: miR125a/hexokinase 2 pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell assay
• Mechanism Description: BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Colorectal cancer [66]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Oxaliplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: HCT116-OxR cells; Colon; Homo sapiens (Human); CVCL_0291
• Experiment for Molecule Alteration: Western blot analysis; Immunofluorescence staining assay
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR-506 overexpression in HCT116-OxR cells enhances oxaliplatin sensitivity by inhibiting MDR1/P-gp expression via down-regulation of the Wnt/beta-catenin pathway.

Disease Class: Hepatocellular carcinoma [67]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Oxaliplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-122 inhibits MDR1 expression via suppression of Wnt/beta-catenin pathway, thereby enhancing HCC sensitivity to OXA.

Oxcarbazepine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Epilepsy [68]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Resistant Drug: Oxcarbazepine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: In patients with oxcarbazepine (OXC)-resistant epilepsy, the brain tissue expression of ABCB1 mRNA was found to be inversely correlated with brain levels of 10,11-dihydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide, the active metabolite of OXC, indicating that Pgp may play a role in the pharmacoresistance to OXC by causing insufficient concentrations of its active metabolite at neuronal targets.

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Ovarian cancer [69]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: UCA1/miR129/ABCB1 signaling pathway; Regulation; hsa05206
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: Hey A8 cells; Ovary; Homo sapiens (Human); CVCL_8878
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: ABCB1 up-regulated by UCA1/miR-129 axis contributed to PTX resistance in PTX-resistant OC cells.

Disease Class: Ovarian cancer [70]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The upregulation of P-gp cause ovarian cancer cells pumping drug substance outside to reduce cytotoxicity presented and enhances the resistance of paclitaxe.

Disease Class: Colorectal carcinoma [71]

• Resistant Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: The transient exposure to digoxin for 24 h was found to induce MDR1 mRNA in Caco-2 cells. Here, a digoxin-tolerant Caco-2 subline (Caco/DX) was newly established by the continuous exposure of Caco-2 cells to digoxin, and the effects of continuous exposure to digoxin on MDR1 were examined. The 50% growth inhibitory concentration (IC(50)) values for digoxin in Caco-2 and Caco/DX cells were 17.2 and 81.4 nM, respectively. The IC(50) values for paclitaxel, an MDR1 substrate, were 1.0 and 547 nM, respectively, whereas the cytotoxicity of 5-fluorouracil was comparable in both.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [72]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7/PR cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: Down-regulation of LncRNA RP11-770J1.3 and TMEM25 enhanced the sensitivity of MCF-7/PR cells to paclitaxel, and inhibited the expression of MRP, BCRP and MDR1/P-gp.

Disease Class: Solid tumour/cancer [38]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Disease Class: Colorectal cancer [73]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Inhibition of LINC00473 in vivo could overcome the Taxol resistance of CRC cells, could recover the expression of tumor suppressor miR-15a and chemotherapy-induced tumor regression while the BCL-2-related anti-apoptosis pathway was activated and the multidrug-resistant (MDR) genes LRP, MDR1 were up-regulated by LINC00473.

Disease Class: Ovarian cancer [69]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: UCA1/miR129/ABCB1 signaling pathway; Regulation; hsa05206
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: Hey A8 cells; Ovary; Homo sapiens (Human); CVCL_8878
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: ABCB1 up-regulated by UCA1/miR-129 axis contributed to PTX resistance in PTX-resistant OC cells.

Disease Class: Ovarian cancer [18]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Both A2780/DDP and A2780/Taxol cells expressed miR-186 at lower levels than A2780. miR-186 overexpression increased the sensitivity of ovarian cancer cell lines to paclitaxel and cisplatin compared with the negative control or mock cells, miR-186 transfection induced cell apoptosis while anti-miR-186 transfection reduced cell apoptosis, suggesting that miR-186 may inhibit the development of drug resistance in ovarian cancer cells. miR-186 overexpression may increase the sensitivity of ovarian cancer cells to paclitaxel by targeting ABCB1 and modulating GST-Pi.

Disease Class: Ovarian cancer [19]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-133b increases ovarian cancer cell sensitivity to cisplatin and paclitaxel by decreasing GST-Pi and MDR1 expression.

Disease Class: Hepatocellular carcinoma [45]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: Skhep1 cells; Liver; Homo sapiens (Human); CVCL_0525
• In Vitro Model: HCC3 cells; Liver; Homo sapiens (Human); CVCL_0C57
• In Vitro Model: LM-6 cells; Liver; Homo sapiens (Human); CVCL_7680
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: miR-223 targeted ABCB1 3'UTR directly, and miR-223 down-regulated ABCB1 at both mRNA and protein levels. The over-expression of miR-223 increased the HCC cellsensitivity to anticancer drugs, and the inhibition of miR-223 had the opposite effect. Importantly, the over-expression or silencingof ABCB1 can rescue the cell response to the anticancer drugs mediated by miR-223 over-expression or inhibition.

Perphenazine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glioblastoma [74]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Sensitive Drug: Perphenazine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• In Vitro Model: SHI-1 cells; Bone marrow; Homo sapiens (Human); CVCL_2191
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The present study explored the effects of perphenazine and prochlorperazine on the levels of ABCB1, ABCG2, E-cadherin, alpha-tubulin and integrins (alpha3, alpha5, and beta1), as well as on the migratory and invasive ability of U87-MG cells. The results suggested that perphenazine and prochlorperazine may modulate the expression levels of multidrug resistance proteins (they decreased ABCB1 and increased ABCG2 expression), E-cadherin, alpha-tubulin and integrins, and could impair the migration and invasion of U-87 MG cells.

Phenobarbital

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Status epilepticus [75]

• Resistant Disease: Status epilepticus [ICD-11: 8A66.0]
• Resistant Drug: Phenobarbital
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Pgp is involved in the resistance to phenytoin and phenobarbital but not diazepam.

Phenytoin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Epilepsy [68]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Resistant Drug: Phenytoin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Comparing phenytoin brain/plasma ratio in mdr1 knockout mice with this ratio in mice with kainate-induced overexpression of Pgp indicated that Pgp can affect up to about 70% of phenytoin brain uptake. In epileptic rats, van Vliet et al reported decreased brain levels of phenytoin that were restricted to brain regions with increased expression of Pgp, which could be counteracted by inhibiting Pgp.

Disease Class: Status epilepticus [75]

• Resistant Disease: Status epilepticus [ICD-11: 8A66.0]
• Resistant Drug: Phenytoin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Pgp is involved in the resistance to phenytoin and phenobarbital but not diazepam.

Prednisolone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Nephrotic syndrome [76]

• Resistant Disease: Nephrotic syndrome [ICD-11: GB41.0]
• Resistant Drug: Prednisolone
• Molecule Alteration: SNP; c.G2677T/A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood sample; .
• Experiment for Molecule Alteration: PCR-RFLP
• Mechanism Description: MDR1 G2677T/A polymorphism was significantly associated with steroid resistance.

Disease Class: Nephrotic syndrome [76]

• Resistant Disease: Nephrotic syndrome [ICD-11: GB41.0]
• Resistant Drug: Prednisolone
• Molecule Alteration: SNP; c.G2677T/A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood sample; .
• Experiment for Molecule Alteration: PCR-RFLP
• Mechanism Description: MDR1 G2677T/A polymorphism was significantly associated with steroid resistance.

Prednisone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Primary immune thrombocytopenia [77]

• Resistant Disease: Primary immune thrombocytopenia [ICD-11: 3B64.0]
• Resistant Drug: Prednisone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: B-cells; Peripheral blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Rhodamine 123 efflux assay
• Mechanism Description: The functional activity and mRNA level of P-gp were significantly higher in glucocorticoids-nonresponsive patients than in glucocorticoids-responsive patients with primary immune thrombocytopenia.

Disease Class: Myasthenia gravis [78]

• Resistant Disease: Myasthenia gravis [ICD-11: 8C60.0]
• Resistant Drug: Prednisone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lymphocyte; Lymph node; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Prednisone (PDN) is transported by P-glycoprotein (P-gp). P-gp overfunction has been associated with resistance to several drug.

Disease Class: Myasthenia gravis [78]

• Resistant Disease: Myasthenia gravis [ICD-11: 8C60.0]
• Resistant Drug: Prednisone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lymphocyte; Lymph node; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Prednisone (PDN) is transported by P-glycoprotein (P-gp). P-gp overfunction has been associated with resistance to several drug.

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Prednisone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Prochlorperazine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glioblastoma [74]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Sensitive Drug: Prochlorperazine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: SHI-1 cells; Bone marrow; Homo sapiens (Human); CVCL_2191
• Experiment for Molecule Alteration: Western blotting analysis; RNA-sequencing analysis
• Experiment for Drug Resistance: Wound healing assay;Transwell assay
• Mechanism Description: Prochlorperazine may modulate the expression levels of multidrug resistance proteins (they decreased ABCB1 and increased ABCG2 expression), E-cadherin, alpha-tubulin and integrins, and could impair the migration and invasion of U-87 MG cells.

Riluzole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Amyotrophic lateral sclerosis [79]

• Resistant Disease: Amyotrophic lateral sclerosis [ICD-11: 8B60.0]
• Resistant Drug: Riluzole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: bEND.3 cells; Brain; Homo sapiens (Human); CVCL_0170
• In Vitro Model: C8D1A cells; Colon; Mus musculus (Mouse); CVCL_6379
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: High-performance liquid chromatography
• Mechanism Description: Riluzole is moderately effective for ALS patients and prolongs survival by only three months. According to previous studies, increased P-gp transporter activity and expression are induced by ALS. As riluzole is a substrate of P-gp, the inductions potentially limit the brain distribution of riluzole and further promote drug resistance in the later stage of ALS disease.

Disease Class: Spinal cord injury [80]

• Resistant Disease: Spinal cord injury [ICD-11: 8C21.0]
• Resistant Drug: Riluzole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Abcb1a Knockout rats model; Mus musculus
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: High performance liquid chromatography assay
• Mechanism Description: Riluzole spinal cord disposition was significantly higher in knockout rats than in WT rats at 10 days post-spinal cord injury (p=0.019), confirming that Pgp plays a critical role in diminishing spinal cord riluzole disposition following spinal cord injury.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Amyotrophic lateral sclerosis [79]

• Sensitive Disease: Amyotrophic lateral sclerosis [ICD-11: 8B60.0]
• Sensitive Drug: Riluzole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: bEND.3 cells; Brain; Homo sapiens (Human); CVCL_0170
• In Vitro Model: C8D1A cells; Colon; Mus musculus (Mouse); CVCL_6379
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: High-performance liquid chromatography
• Mechanism Description: BEND.3 Cells were treated with riluzole and verapamil liposomes at different doses and time durations to determine the inhibitory levels of P-gp. In the buffer control treatment, the expression of P-gp was noted as a baseline level (100%). After the exposure to 5, 10, 20, 30, and 40 ug/ml cocktail liposomes for 48 h, bEND.3 cells resulted in a distinct decrease of P-gp expression with 93.0 plus or minus 5.2%, 85.8 plus or minus 4.7%, 50.3 plus or minus 5.6% 26.2 plus or minus 5.1%, and 20.8 plus or minus 4.9% of the baseline level, respectively. The extent of the decrease was linearly dependent on the concentration of verapamil in formulations (5 to 30 ug/ml), while inhibited levels of P-gp by 30 ug/ml and 40 ug/ml of verapamil cocktail liposome were not significantly different.

Steroid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Idiopathic nephrotic syndrome [81]

• Resistant Disease: Idiopathic nephrotic syndrome [ICD-11: GB41.1]
• Resistant Drug: Steroid
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The up-regualtion of mdr1 led to steroid resistance in the idiopathic nephrotic syndrome.

Disease Class: Idiopathic nephrotic syndrome [81]

• Resistant Disease: Idiopathic nephrotic syndrome [ICD-11: GB41.1]
• Resistant Drug: Steroid
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The up-regualtion of mdr1 led to steroid resistance in the idiopathic nephrotic syndrome.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glioblastoma [82]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Upregulation of TUSC7,which acted by directly targeting and silencing expression of miR-10a gene, suppressed both TMZ resistance and expression of multidrug resistance protein 1 (MDR1) in U87TR cells,, and miR-10a mediated TUSC7-induced inhibition on TMZ resistance in U87TR cells.

Disease Class: Malignant glioma [83]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Knockdown of long noncoding RNA H19 sensitizes human glioma cells to temozolomide therapy.the expression level of H19 transcripts was increased compared to wild-type or nonresistant clones.Furthermore, the reduced expression of H19 altered major drug resistance genes, such as ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP), both at the mRNA and protein levels. Taken together, these findings suggest that H19 plays an important role in the development of TMZ resistance, and may represent a novel therapeutic target for TMZ-resistant gliomas.Our results suggested that knockdown of H19 significantly downregulated the expression of these drug-resistant genes, both at the mRNA (P<0.001 vs respective control siRNA) and protein levels. These data confirm that the H19-induced TMZ resistance is in part mediated by MDR, MRP, and ABCG2.

Disease Class: Glioblastoma [84]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: Glioblastoma tissue; .
• Experiment for Molecule Alteration: Real-time PCR
• Experiment for Drug Resistance: Patient survival time
• Mechanism Description: In the chemosensitive MDR1-negative parental cell line k562 10 ug/ml temozolomide resulted in pronounced cell death with only 47.1% surviving 48 h compared with the control. In contrast, in the highly MDR1-expressing resistant subline k562-VP16, cell death was significantly lower after exposure to temozolomide with 73.4% surviving 48 h (P = 0.002). Addition of a nontoxic dose of the MDR1-modulator cyclosporine A (1 uM) to temozolomide resulted in a trend towards restoration of chemosensitivity in the resistant MDR1-expressing cell line.

Disease Class: Chronic myelogenous leukemia [84]

• Resistant Disease: Chronic myelogenous leukemia [ICD-11: 2A20.3]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562-VP16 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Real-time PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: In the chemosensitive MDR1-negative parental cell line k562 10 ug/ml temozolomide resulted in pronounced cell death with only 47.1% surviving 48 h compared with the control. In contrast, in the highly MDR1-expressing resistant subline k562-VP16, cell death was significantly lower after exposure to temozolomide with 73.4% surviving 48 h (P = 0.002). Addition of a nontoxic dose of the MDR1-modulator cyclosporine A (1 uM) to temozolomide resulted in a trend towards restoration of chemosensitivity in the resistant MDR1-expressing cell line.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glioblastoma [84]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: Glioblastoma tissue; .
• Experiment for Molecule Alteration: Real-time PCR
• Experiment for Drug Resistance: Patient survival time
• Mechanism Description: In the chemosensitive MDR1-negative parental cell line k562 10 ug/ml temozolomide resulted in pronounced cell death with only 47.1% surviving 48 h compared with the control. In contrast, in the highly MDR1-expressing resistant subline k562-VP16, cell death was significantly lower after exposure to temozolomide with 73.4% surviving 48 h (P = 0.002). Addition of a nontoxic dose of the MDR1-modulator cyclosporine A (1 uM) to temozolomide resulted in a trend towards restoration of chemosensitivity in the resistant MDR1-expressing cell line.

Disease Class: Chronic myelogenous leukemia [84]

• Sensitive Disease: Chronic myelogenous leukemia [ICD-11: 2A20.3]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562-VP16 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Real-time PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: In the chemosensitive MDR1-negative parental cell line k562 10 ug/ml temozolomide resulted in pronounced cell death with only 47.1% surviving 48 h compared with the control. In contrast, in the highly MDR1-expressing resistant subline k562-VP16, cell death was significantly lower after exposure to temozolomide with 73.4% surviving 48 h (P = 0.002). Addition of a nontoxic dose of the MDR1-modulator cyclosporine A (1 uM) to temozolomide resulted in a trend towards restoration of chemosensitivity in the resistant MDR1-expressing cell line.

Tocotrienol

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [85]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Tocotrienol
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NF-KappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• Experiment for Molecule Alteration: Quantitative real-time PCR; Western blot analysis; Reporter gene assay of NF-kappaB transcriptional activity assay; MDR1 promoter reporter assay; P-gp activity assay
• Experiment for Drug Resistance: Reversal effect assay
• Mechanism Description: Gamma-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the gamma-Tocotrienol-NF-kappaB-P-gp axis. gamma-Tocotrienol effectively suppressed mdr1 promoter activity and the efflux of P-gp. gamma-Tocotrienol inhibited NF-kappaB activation and reduced NF-kappaB transcriptional activity.

Disease Class: Breast cancer [85]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Tocotrienol
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NF-KappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• Experiment for Molecule Alteration: Quantitative real-time PCR; Western blot analysis; Reporter gene assay of NF-kappaB transcriptional activity assay; MDR1 promoter reporter assay; P-gp activity assay
• Experiment for Drug Resistance: Reversal effect assay
• Mechanism Description: Gamma-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the gamma-Tocotrienol-NF-kappaB-P-gp axis. gamma-Tocotrienol effectively suppressed mdr1 promoter activity and the efflux of P-gp. gamma-Tocotrienol inhibited NF-kappaB activation and reduced NF-kappaB transcriptional activity.

Vardenafil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Solid tumour/cancer [86]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Vardenafil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SJG 2 cells; Ora cavity; Homo sapiens (Human); CVCL_WV26
• In Vitro Model: ATCC 293T cells; Fetal kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis; Immunofluorescence analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Vardenafil reverses ABCB1-mediated MDR by directly blocking the drug efflux function of ABCB1.

Verapamil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Hypertrophic scar [52]

• Resistant Disease: Hypertrophic scar [ICD-11: EE60.0]
• Resistant Drug: Verapamil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Hypertrophic scar tissue isolates; .
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.

Vinblastine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glioma [29]

• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Resistant Drug: Vinblastine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Disease Class: Colorectal carcinoma [29]

• Resistant Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Resistant Drug: Vinblastine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Disease Class: Squamous cell carcinoma [29]

• Resistant Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Resistant Drug: Vinblastine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• In Vitro Model: KB-V1 cells; Mouth; Homo sapiens (Human); CVCL_2089
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Disease Class: Cervical carcinoma [29]

• Resistant Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Resistant Drug: Vinblastine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Chronic myeloid leukemia [26]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Sensitive Drug: Vinblastine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: K562-R cells; Pleural effusion; Homo sapiens (Human); CVCL_5950
• In Vitro Model: NCI-H460/VBL cells; Bone marrow; Homo sapiens (Human); CVCL_0459
• In Vivo Model: SCID beige mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: In ABCB1-overexpressing cell lines, HG-829 significantly enhanced cytotoxicity to daunorubicin, paclitaxel, vinblastine, vincristine, and etoposide. Coadministration of HG-829 fully restored in vivo antitumor activity of daunorubicin in mice without added toxicity. Functional assays showed that HG-829 is not a Pgp substrate or competitive inhibitor of Pgp-mediated drug efflux but rather acts as a noncompetitive modulator of P-glycoprotein transport function.

Disease Class: Renal cell carcinoma [27]

• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Sensitive Drug: Vinblastine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Flp-In-293/Mock cells; Kidney; Homo sapiens (Human); CVCL_U421
• In Vitro Model: Flp-In-293/ABCB1 cells; Kidney; Homo sapiens (Human); CVCL_U421
• Experiment for Molecule Alteration: ATPase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.

Vincristine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Burkitt lymphoma [28]

• Resistant Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Disease Class: Ependymoma [53]

• Resistant Disease: Ependymoma [ICD-11: 2A00.05]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Disease Class: Keloid [64]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

Disease Class: Keloid [64]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

Disease Class: Anaplastic astrocytoma [5]

• Resistant Disease: Anaplastic astrocytoma [ICD-11: 2A00.04]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Protein kinase C signaling pathways; Inhibition; hsa04310
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: Oncotech EDR assay
• Mechanism Description: On the other hand, the frequency of LDR that we noted for paclitaxel (20%) and vincristine (20%) was similar to the clinical response rates for these compounds. These data suggest that although MDR1 expression by glial tumors may not be the dominant direct cellular process responsible for tumor resistance to natural products, other mechanisms are present that diminish their activity. The clinical mechanisms of natural product resistance may be a multifactorial function of endothelial expression of MDR1 at the blood-brain barrier in conjunction with glial tumor cell expression of alternative efflux pumps, such as MRP, altered tubulin with lower affinity binding sites, and/or protein kinase C signaling pathways that suppress apoptosis.

Disease Class: Malignant glioma [5]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Malignant gliomas tissue; .
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: EDR assay
• Mechanism Description: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Gastric cancer [40], [41]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay assay
• Mechanism Description: MRUL depletion enhances the chemosensitivity of stomach cancer cells via inhibiting ABCB1 expression and increasing cell apoptosis. And The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Disease Class: Esophageal squamous cell carcinoma [20], [21]

• Sensitive Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: ECA-109 cells; Esophagus; Homo sapiens (Human); CVCL_6898
• In Vitro Model: TE13 cells; Esophageal; Homo sapiens (Human); CVCL_4463
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: Down-regulation of miR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax. And down-regulation of miR-27a significantly decreased expression of MDR1, but did not alter the expression of MRP, miR-27a could possibly mediate drug resistance, at least in part through regulation of MDR1 and apoptosis.

Disease Class: Gastric cancer [22]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Disease Class: Leukemia [23]

• Sensitive Disease: Leukemia [ICD-11: 2B33.6]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-138 was found up-regulated in the vincristine-induced multidrug resistance (MDR) leukemia cell line HL-60/VCR as compared with HL-60 cells. Up-regulation of miR-138 could reverse resistance of both P-glycoprotein-related and P-glycoprotein-non-related drugs on HL-60/VCR cells, and promote adriamycin-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of adriamycin.

Disease Class: Burkitt lymphoma [28]

• Sensitive Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Disease Class: Ependymoma [53]

• Sensitive Disease: Ependymoma [ICD-11: 2A00.05]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Disease Class: Ependymoma [53]

• Sensitive Disease: Ependymoma [ICD-11: 2A00.05]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: BXD-1425EPN cells; Embryo; Homo sapiens (Human); CVCL_Y105
• In Vitro Model: EPN1 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EPN7R cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: DKFZ-EP1 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).

Disease Class: Renal cell carcinoma [27]

• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Flp-In-293/Mock cells; Kidney; Homo sapiens (Human); CVCL_U421
• In Vitro Model: Flp-In-293/ABCB1 cells; Kidney; Homo sapiens (Human); CVCL_U421
• Experiment for Molecule Alteration: ATPase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.

Vindesine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Esophageal squamous cell carcinoma [87]

• Resistant Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Resistant Drug: Vindesine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16-F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vitro Model: BHT101 cells; Lymph node; Homo sapiens (Human); CVCL_1085
• In Vitro Model: BHT-101 cells; Thyroid gland; Homo sapiens (Human); CVCL_1085
• In Vitro Model: C2C12 mouse skeletal muscle cells; Skeletal muscle; Mus musculus (Mouse); CVCL_0188
• In Vitro Model: C6 cells; Brain; Rattus norvegicus (Rat); CVCL_0194
• In Vitro Model: C643 cells; Thyroid gland; Homo sapiens (Human); CVCL_5969
• In Vitro Model: Caco-2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: CAL-1 [Human plasmacytoid dendritic] cells; Pleural effusion; Homo sapiens (Human); CVCL_5G46
• Experiment for Molecule Alteration: DNA and RNA analysis
• Experiment for Drug Resistance: Colony Formation
• Mechanism Description: In SH-1-V8 cells, cellular accumulation of vincristine decreased and an MDR reversal agent, cepharanthine, potentiated the cytoci-dal action of vindesine. The expression of MDR 1 mRNA was enhanced and amplification of the MDR1 gene was observed in clones SH-1-V4, SH-1-V5, SH-1-V6, SH-1-V7 and SH-1-V8; expression of MDR1 mRNA was detectable without gene amplification in the remaining 3 clones. The enhanced expression of the MDR1 gene may be involved in the acquisition of vindesine resistance in human esophageal cancer cells.

Discontinued Drug(s) 1 drug(s) in total

Cevipabulin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glioma [29]

• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Resistant Drug: Cevipabulin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Disease Class: Colorectal carcinoma [29]

• Resistant Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Resistant Drug: Cevipabulin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Disease Class: Squamous cell carcinoma [29]

• Resistant Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Resistant Drug: Cevipabulin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• In Vitro Model: KB-V1 cells; Mouth; Homo sapiens (Human); CVCL_2089
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Disease Class: Cervical carcinoma [29]

• Resistant Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Resistant Drug: Cevipabulin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Investigative Drug(s) 10 drug(s) in total

Actinomycin D

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Pituitary adenoma [25]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Actinomycin D
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

Ampicillin-sulbactam

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Staphylococcus infection [1]

• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Resistant Drug: Ampicillin-sulbactam
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to ampicillin-sulbactam resistance in the staphylococcus infection.

Bucillamine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Rheumatoid arthritis [3]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Bucillamine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Corticosteroids

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Lupus erythematosus [62]

• Resistant Disease: Lupus erythematosus [ICD-11: 4A40.0]
• Resistant Drug: Corticosteroids
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Flow cytometry assay
• Mechanism Description: Several studies on patients with systemic autoimmune diseases in particular SLE, RA and PsA have demonstrated a significant correlation between P-gp expression/function, disease activity and the development of resistance to immunosuppressive therapy.

Disease Class: Lupus erythematosus [62]

• Resistant Disease: Lupus erythematosus [ICD-11: 4A40.0]
• Resistant Drug: Corticosteroids
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Flow cytometry assay
• Mechanism Description: Several studies on patients with systemic autoimmune diseases in particular SLE, RA and PsA have demonstrated a significant correlation between P-gp expression/function, disease activity and the development of resistance to immunosuppressive therapy.

Disorazole A1

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [88]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Disorazole A1
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MCF-7/MDR cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Disease Class: Cervical carcinoma [88]

• Resistant Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Resistant Drug: Disorazole A1
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Disease Class: Lung adenocarcinoma [88]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Disorazole A1
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/EpoB40 cells; Lung; Homo sapiens (Human); CVCL_4Z15
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Disorazole C1

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [88]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Disorazole C1
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MCF-7/MDR cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Disease Class: Cervical carcinoma [88]

• Resistant Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Resistant Drug: Disorazole C1
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Disease Class: Lung adenocarcinoma [88]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Disorazole C1
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/EpoB40 cells; Lung; Homo sapiens (Human); CVCL_4Z15
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Gardiquimod

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Melanoma [89]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Gardiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Disease Class: Prostate cancer [89]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Gardiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Disease Class: Breast cancer [89]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Gardiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Imiquimod

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Melanoma [89]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Imiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Disease Class: Prostate cancer [89]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Imiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Disease Class: Breast cancer [89]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Imiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Puromycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Pituitary adenoma [25]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Puromycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

Resiquimod

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Melanoma [89]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Resiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Disease Class: Prostate cancer [89]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Resiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Disease Class: Breast cancer [89]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Resiquimod
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin Cell Viability Assay
• Mechanism Description: Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 01

HIV infection [ICD-11: 1C62]

Differential expression of molecule in resistant diseases

• The Studied Tissue: White matter
• The Specified Disease: HIV infection
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.39E-01; Fold-change: 1.21E-01; Z-score: 4.34E-01

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.39E-11; Fold-change: -2.93E-01; Z-score: -6.11E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.84E-01; Fold-change: -1.02E+00; Z-score: -2.26E+00
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.21E-01; Fold-change: -1.31E-01; Z-score: -9.67E-02
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.31E-02; Fold-change: -4.89E-01; Z-score: -9.87E-01

Chronic myeloid leukemia [ICD-11: 2A20]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Whole blood
• The Specified Disease: Myelofibrosis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.73E-01; Fold-change: 9.15E-02; Z-score: 3.06E-01
• The Studied Tissue: Whole blood
• The Specified Disease: Polycythemia vera
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.18E-01; Fold-change: -1.11E-01; Z-score: -4.02E-01

Acute myeloid leukemia [ICD-11: 2A60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Acute myeloid leukemia
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.70E-06; Fold-change: -5.80E-02; Z-score: -1.98E-01

Oral squamous cell carcinoma [ICD-11: 2B6E]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Oral tissue
• The Specified Disease: Oral squamous cell carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.35E-03; Fold-change: -1.49E-01; Z-score: -4.36E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.16E-31; Fold-change: -6.48E-01; Z-score: -1.96E+00

Esophageal cancer [ICD-11: 2B70]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Esophagus
• The Specified Disease: Esophageal cancer
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.03E-03; Fold-change: -6.46E-01; Z-score: -3.13E+00

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.42E-03; Fold-change: 3.68E-01; Z-score: 3.09E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.31E-03; Fold-change: 2.52E-01; Z-score: 5.13E-01

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.54E-01; Fold-change: 1.87E-01; Z-score: 4.30E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.52E-13; Fold-change: -3.21E-01; Z-score: -7.40E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 6.68E-01; Fold-change: 2.98E-01; Z-score: 3.46E+00

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.12E-33; Fold-change: -8.30E-01; Z-score: -1.04E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.12E-24; Fold-change: -9.94E-01; Z-score: -1.11E+00

Melanoma [ICD-11: 2C30]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Skin
• The Specified Disease: Melanoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.98E-02; Fold-change: -4.69E-01; Z-score: -5.99E-01

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.61E-73; Fold-change: -1.15E+00; Z-score: -1.66E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.48E-13; Fold-change: -1.04E+00; Z-score: -1.79E+00

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.53E-04; Fold-change: -6.93E-01; Z-score: -2.04E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.32E-02; Fold-change: -6.33E-01; Z-score: -5.21E-01

Cervical cancer [ICD-11: 2C77]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Cervix uteri
• The Specified Disease: Cervical cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.78E-01; Fold-change: -1.00E-02; Z-score: -2.13E-02

Prostate cancer [ICD-11: 2C82]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Prostate
• The Specified Disease: Prostate cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.55E-01; Fold-change: 4.83E-01; Z-score: 5.66E-01

Kidney cancer [ICD-11: 2C90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Kidney
• The Specified Disease: Kidney cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.04E-02; Fold-change: -1.13E+00; Z-score: -1.00E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.90E-49; Fold-change: -1.68E+00; Z-score: -3.26E+00

Pituitary cancer [ICD-11: 2F37]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pituitary
• The Specified Disease: Pituitary cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.27E-03; Fold-change: 4.49E-01; Z-score: 1.31E+00
• The Studied Tissue: Pituitary
• The Specified Disease: Pituitary gonadotrope tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.32E-01; Fold-change: -1.48E-01; Z-score: -3.76E-01

ICD Disease Classification 03

Thrombocytopenia [ICD-11: 3B64]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Whole blood
• The Specified Disease: Thrombocytopenia
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.81E-01; Fold-change: 5.10E-02; Z-score: 4.59E-02

ICD Disease Classification 04

Lupus erythematosus [ICD-11: 4A40]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Whole blood
• The Specified Disease: Lupus erythematosus
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.63E-15; Fold-change: -6.34E-01; Z-score: -9.11E-01

ICD Disease Classification 08

Epilepsy [ICD-11: 8A60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Peritumoral cortex tissue
• The Specified Disease: Epilepsy
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 2.76E-01; Fold-change: -2.17E-01; Z-score: -7.28E-01

Amyotrophic lateral sclerosis [ICD-11: 8B60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Cervical spinal cord
• The Specified Disease: Amyotrophic lateral sclerosis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.08E-01; Fold-change: -2.87E-01; Z-score: -5.57E-01
• The Studied Tissue: Skin
• The Specified Disease: Amyotrophic lateral sclerosis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.05E-01; Fold-change: 1.60E-01; Z-score: 1.37E+00

ICD Disease Classification 14

Psoriasis [ICD-11: EA90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Skin
• The Specified Disease: Psoriasis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.00E-01; Fold-change: 2.57E-02; Z-score: 6.18E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.81E-09; Fold-change: -3.22E-01; Z-score: -7.89E-01

ICD Disease Classification 15

Rheumatoid arthritis [ICD-11: FA20]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Peripheral blood
• The Specified Disease: Rheumatoid arthritis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.89E-02; Fold-change: 1.21E-02; Z-score: 2.54E-02
• The Studied Tissue: Synovial tissue
• The Specified Disease: Rheumatoid arthritis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.45E-02; Fold-change: -1.49E-01; Z-score: -3.47E-01

References

• Ref 1: Pathogen characteristics reveal novel antibacterial approaches for interstitial lung disease .Pulm Pharmacol Ther. 2014 Dec;29(2):250-4. doi: 10.1016/j.pupt.2014.03.005. Epub 2014 Apr 1. 10.1016/j.pupt.2014.03.005
• Ref 2: Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement .J Thromb Thrombolysis. 2018 Apr;45(3):463-465. doi: 10.1007/s11239-018-1636-z. 10.1007/s11239-018-1636-z
• Ref 3: Drug-resistance in rheumatoid arthritis: the role of p53 gene mutations, ABC family transporters and personal factors .Curr Opin Pharmacol. 2020 Oct;54:59-71. doi: 10.1016/j.coph.2020.08.002. Epub 2020 Sep 14. 10.1016/j.coph.2020.08.002
• Ref 4: Association of ABCB1 polymorphisms with carbamazepine metabolism and resistance in epilepsy: A meta-analysis .Epilepsy Res. 2021 Nov;177:106785. doi: 10.1016/j.eplepsyres.2021.106785. Epub 2021 Oct 7. 10.1016/j.eplepsyres.2021.106785
• Ref 5: In vitro drug response and molecular markers associated with drug resistance in malignant gliomas .Clin Cancer Res. 2006 Aug 1;12(15):4523-32. doi: 10.1158/1078-0432.CCR-05-1830. 10.1158/1078-0432.CCR-05-1830
• Ref 6: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis. Eur Rev Med Pharmacol Sci. 2019 May;23(10):4185-4191. doi: 10.26355/eurrev_201905_17921.
• Ref 7: Knockdown of long non-coding RNA HOTAIR sensitizes hepatocellular carcinoma cell to cisplatin by suppressing the STAT3/ABCB1 signaling pathway. Oncol Lett. 2017 Dec;14(6):7986-7992. doi: 10.3892/ol.2017.7237. Epub 2017 Oct 20.
• Ref 8: Autophagy regulated by lncRNA HOTAIR contributes to the cisplatin-induced resistance in endometrial cancer cells. Biotechnol Lett. 2017 Oct;39(10):1477-1484. doi: 10.1007/s10529-017-2392-4. Epub 2017 Jul 18.
• Ref 9: Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1. Int J Biol Sci. 2018 Feb 12;14(3):321-330. doi: 10.7150/ijbs.24360. eCollection 2018.
• Ref 10: Effect of microRNA-21 on multidrug resistance reversal in A549/DDP human lung cancer cells. Mol Med Rep. 2015 Jan;11(1):682-90. doi: 10.3892/mmr.2014.2662. Epub 2014 Oct 15.
• Ref 11: MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-Beta/Smad2/STAT3/STAT5 pathway. Mol Med Rep. 2015 May;11(5):3854-9. doi: 10.3892/mmr.2015.3181. Epub 2015 Jan 12.
• Ref 12: MiR-130a and MiR-374a Function as Novel Regulators of Cisplatin Resistance in Human Ovarian Cancer A2780 Cells. PLoS One. 2015 Jun 4;10(6):e0128886. doi: 10.1371/journal.pone.0128886. eCollection 2015.
• Ref 13: Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance. Biochem Biophys Res Commun. 2015 Jul 3;462(3):227-32. doi: 10.1016/j.bbrc.2015.04.121. Epub 2015 May 5.
• Ref 14: MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1. Oncotarget. 2017 May 16;8(20):33621-33630. doi: 10.18632/oncotarget.16834.
• Ref 15: MicroRNA-595 sensitizes ovarian cancer cells to cisplatin by targeting ABCB1. Oncotarget. 2016 Dec 27;7(52):87091-87099. doi: 10.18632/oncotarget.13526.
• Ref 16: miR-381 overcomes cisplatin resistance in breast cancer by targeting MDR1. Cell Biol Int. 2019 Jan;43(1):12-21. doi: 10.1002/cbin.11071.
• Ref 17: The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway. Exp Ther Med. 2018 Jun;15(6):4885-4889. doi: 10.3892/etm.2018.6052. Epub 2018 Apr 11.
• Ref 18: MicroRNA-186 induces sensitivity of ovarian cancer cells to paclitaxel and cisplatin by targeting ABCB1. J Ovarian Res. 2015 Dec 2;8:80. doi: 10.1186/s13048-015-0207-6.
• Ref 19: MicroRNA-133b targets glutathione S-transferase Pi expression to increase ovarian cancer cell sensitivity to chemotherapy drugs. Drug Des Devel Ther. 2015 Sep 16;9:5225-35. doi: 10.2147/DDDT.S87526. eCollection 2015.
• Ref 20: Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Dig Dis Sci. 2010 Sep;55(9):2545-51. doi: 10.1007/s10620-009-1051-6. Epub 2009 Dec 4.
• Ref 21: The prognostic and chemotherapeutic value of miR-296 in esophageal squamous cell carcinoma. Ann Surg. 2010 Jun;251(6):1056-63. doi: 10.1097/SLA.0b013e3181dd4ea9.
• Ref 22: miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene. 2014 Jun 19;33(25):3267-76. doi: 10.1038/onc.2013.297. Epub 2013 Jul 29.
• Ref 23: miR-138 might reverse multidrug resistance of leukemia cells. Leuk Res. 2010 Aug;34(8):1078-82. doi: 10.1016/j.leukres.2009.10.002. Epub 2009 Nov 6.
• Ref 24: Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine. J Clin Psychopharmacol. 2016 Jun;36(3):257-61. doi: 10.1097/JCP.0000000000000495.
• Ref 25: Characterization of multidrug-resistant pituitary tumor cells .Endocrinology. 1992 Jun;130(6):3246-56. doi: 10.1210/endo.130.6.1350759. 10.1210/endo.130.6.1350759
• Ref 26: HG-829 is a potent noncompetitive inhibitor of the ATP-binding cassette multidrug resistance transporter ABCB1. Cancer Res. 2012 Aug 15;72(16):4204-13. doi: 10.1158/0008-5472.CAN-12-0743. Epub 2012 Jul 3.
• Ref 27: Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance .Phytomedicine. 2018 Dec 1;51:112-119. doi: 10.1016/j.phymed.2018.06.030. Epub 2018 Jun 20. 10.1016/j.phymed.2018.06.030
• Ref 28: Dasatinib reverses drug resistance by downregulating MDR1 and Survivin in Burkitt lymphoma cells .BMC Complement Med Ther. 2020 Mar 14;20(1):84. doi: 10.1186/s12906-020-2879-8. 10.1186/s12906-020-2879-8
• Ref 29: TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. doi: 10.1158/0008-5472.CAN-07-1420.
• Ref 30: LncRNA H19 is a major mediator of doxorubicin chemoresistance in breast cancer cells through a cullin4A-MDR1 pathway. Oncotarget. 2017 Sep 21;8(54):91990-92003. doi: 10.18632/oncotarget.21121. eCollection 2017 Nov 3.
• Ref 31: Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer. Med Oncol. 2012 Dec;29(4):2527-34. doi: 10.1007/s12032-011-0117-4. Epub 2011 Nov 19.
• Ref 32: Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia. J Cell Mol Med. 2011 Oct;15(10):2164-75. doi: 10.1111/j.1582-4934.2010.01213.x.
• Ref 33: Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells. Oncogene. 2007 Jul 19;26(33):4877-81. doi: 10.1038/sj.onc.1210266. Epub 2007 Feb 5.
• Ref 34: Reduced argininosuccinate synthetase expression in refractory sarcomas: Impacts on therapeutic potential and drug resistance .Oncotarget. 2016 Oct 25;7(43):70832-70844. doi: 10.18632/oncotarget.12225. 10.18632/oncotarget.12225
• Ref 35: Knockdown of lncRNA-HOTAIR downregulates the drug-resistance of breast cancer cells to doxorubicin via the PI3K/AKT/mTOR signaling pathway. Exp Ther Med. 2019 Jul;18(1):435-442. doi: 10.3892/etm.2019.7629. Epub 2019 May 29.
• Ref 36: Possible Role of microRNA-122 in Modulating Multidrug Resistance of Hepatocellular Carcinoma. Indian J Clin Biochem. 2018 Jan;33(1):21-30. doi: 10.1007/s12291-017-0651-8. Epub 2017 Apr 21.
• Ref 37: LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1. Oncotarget. 2017 May 18;8(42):71881-71893. doi: 10.18632/oncotarget.17985. eCollection 2017 Sep 22.
• Ref 38: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression. J Cell Mol Med. 2017 Sep;21(9):1929-1943. doi: 10.1111/jcmm.13114. Epub 2017 Apr 14.
• Ref 39: miR-9 regulates the multidrug resistance of chronic myelogenous leukemia by targeting ABCB1. Oncol Rep. 2017 Apr;37(4):2193-2200. doi: 10.3892/or.2017.5464. Epub 2017 Feb 17.
• Ref 40: Long noncoding RNA MRUL promotes ABCB1 expression in multidrug-resistant gastric cancer cell sublines. Mol Cell Biol. 2014 Sep;34(17):3182-93. doi: 10.1128/MCB.01580-13. Epub 2014 Jun 23.
• Ref 41: Methylation of miR-129-5p CpG island modulates multi-drug resistance in gastric cancer by targeting ABC transporters. Oncotarget. 2014 Nov 30;5(22):11552-63. doi: 10.18632/oncotarget.2594.
• Ref 42: Effect of miR-155 knockdown on the reversal of doxorubicin resistance in human lung cancer A549/dox cells. Oncol Lett. 2016 Feb;11(2):1161-1166. doi: 10.3892/ol.2015.3995. Epub 2015 Dec 3.
• Ref 43: Knockdown of microRNA-127 reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human glioma cells. Int J Clin Exp Pathol. 2015 Jun 1;8(6):6107-16. eCollection 2015.
• Ref 44: Role and mechanisms of microRNA 503 in drug resistance reversal in HepG2/ADM human hepatocellular carcinoma cells. Mol Med Rep. 2014 Dec;10(6):3268-74. doi: 10.3892/mmr.2014.2591. Epub 2014 Sep 22.
• Ref 45: MiR-223 modulates multidrug resistance via downregulation of ABCB1 in hepatocellular carcinoma cells. Exp Biol Med (Maywood). 2013 Sep;238(9):1024-32. doi: 10.1177/1535370213497321. Epub 2013 Aug 7.
• Ref 46: Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther. 2008 Jul;7(7):2152-9. doi: 10.1158/1535-7163.MCT-08-0021.
• Ref 47: Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells. Front Oncol. 2021 Oct 6;11:738961. doi: 10.3389/fonc.2021.738961. eCollection 2021.
• Ref 48: The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2020 Oct;77:153280. doi: 10.1016/j.phymed.2020.153280. Epub 2020 Jul 8.
• Ref 49: Inhibition of Chemoresistance in Primary Tumor Cells by Camellia sinensis non fermentatum Extract Noviphenone (NPE ) .Anticancer Res. 2019 Aug;39(8):4101-4110. doi: 10.21873/anticanres.13568. 10.21873/anticanres.13568
• Ref 50: An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. AIDS. 2005 Mar 4;19(4):371-80. doi: 10.1097/01.aids.0000161766.13782.2f.
• Ref 51: Esomeprazole overcomes paclitaxel-resistance and enhances anticancer effects of paclitaxel by inducing autophagy in A549/Taxol cells .Cell Biol Int. 2021 Jan;45(1):177-187. doi: 10.1002/cbin.11481. Epub 2020 Oct 20. 10.1002/cbin.11481
• Ref 52: Disruption of the association between drug transporter and actin cytoskeleton abolishes drug resistance in hypertrophic scar .Oncotarget. 2017 Jan 10;8(2):2617-2627. doi: 10.18632/oncotarget.13734. 10.18632/oncotarget.13734
• Ref 53: A role for ABCB1 in prognosis, invasion and drug resistance in ependymoma .Sci Rep. 2019 Jul 16;9(1):10290. doi: 10.1038/s41598-019-46700-z. 10.1038/s41598-019-46700-z
• Ref 54: Reversal of multidrug resistance by guggulsterone in drug-resistant MCF-7 cell lines .Chemotherapy. 2011;57(1):62-70. doi: 10.1159/000321484. Epub 2011 Feb 1. 10.1159/000321484
• Ref 55: Therapeutic Targeting Steroid Resistant Pro-Inflammatory NK and NKT-Like Cells in Chronic Inflammatory Lung Disease .Int J Mol Sci. 2019 Mar 26;20(6):1511. doi: 10.3390/ijms20061511. 10.3390/ijms20061511
• Ref 56: lncRNA UCA1 Contributes to Imatinib Resistance by Acting as a ceRNA Against miR-16 in Chronic Myeloid Leukemia Cells. DNA Cell Biol. 2017 Jan;36(1):18-25. doi: 10.1089/dna.2016.3533. Epub 2016 Nov 17.
• Ref 57: LncRNA MEG3 Regulates Imatinib Resistance in Chronic Myeloid Leukemia via Suppressing MicroRNA-21. Biomol Ther (Seoul). 2017 Sep 1;25(5):490-496. doi: 10.4062/biomolther.2016.162.
• Ref 58: Ketorolac-fluconazole: A New Combination Reverting Resistance in Candida albicans from Acute Myeloid Leukemia Patients on Induction Chemotherapy: In vitro Study .J Blood Med. 2021 Jun 15;12:465-474. doi: 10.2147/JBM.S302158. eCollection 2021. 10.2147/JBM.S302158
• Ref 59: Effects of ABCB1 (multidrug resistance transporter) gene mutations on disposition and central nervous effects of loperamide in healthy volunteers. Pharmacogenetics. 2003 Nov;13(11):651-60. doi: 10.1097/00008571-200311000-00001.
• Ref 60: Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR-200c/ABCB1 axis. Biochem Biophys Res Commun. 2018 Jan 1;495(1):947-953. doi: 10.1016/j.bbrc.2017.11.121. Epub 2017 Nov 21.
• Ref 61: ABCB1 in dermatology: roles in skin diseases and their treatment .J Mol Med (Berl). 2021 Nov;99(11):1527-1538. doi: 10.1007/s00109-021-02105-y. Epub 2021 Aug 9. 10.1007/s00109-021-02105-y
• Ref 62: P-glycoprotein and drug resistance in systemic autoimmune diseases .Int J Mol Sci. 2014 Mar 20;15(3):4965-76. doi: 10.3390/ijms15034965. 10.3390/ijms15034965
• Ref 63: Drug resistance and treatment failure in leishmaniasis: A 21st century challenge .PLoS Negl Trop Dis. 2017 Dec 14;11(12):e0006052. doi: 10.1371/journal.pntd.0006052. eCollection 2017 Dec. 10.1371/journal.pntd.0006052
• Ref 64: Enhanced expression of membrane transporter and drug resistance in keloid fibroblasts .Hum Pathol. 2012 Nov;43(11):2024-32. doi: 10.1016/j.humpath.2011.12.026. Epub 2012 May 21. 10.1016/j.humpath.2011.12.026
• Ref 65: Long noncoding RNA BLACAT1 modulates ABCB1 to promote oxaliplatin resistance of gastric cancer via sponging miR-361. Biomed Pharmacother. 2018 Mar;99:832-838. doi: 10.1016/j.biopha.2018.01.130. Epub 2018 Feb 20.
• Ref 66: miR-506 enhances the sensitivity of human colorectal cancer cells to oxaliplatin by suppressing MDR1/P-gp expression. Cell Prolif. 2017 Jun;50(3):e12341. doi: 10.1111/cpr.12341. Epub 2017 Feb 19.
• Ref 67: miR-122 enhances sensitivity of hepatocellular carcinoma to oxaliplatin via inhibiting MDR1 by targeting Wnt/Beta-catenin pathway. Exp Mol Pathol. 2019 Feb;106:34-43. doi: 10.1016/j.yexmp.2018.10.009. Epub 2018 Oct 26.
• Ref 68: Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options .Pharmacol Rev. 2020 Jul;72(3):606-638. doi: 10.1124/pr.120.019539. 10.1124/pr.120.019539
• Ref 69: UCA1 confers paclitaxel resistance to ovarian cancer through miR-129/ABCB1 axis. Biochem Biophys Res Commun. 2018 Jul 2;501(4):1034-1040. doi: 10.1016/j.bbrc.2018.05.104. Epub 2018 May 19.
• Ref 70: microRNA 490-3P enhances the drug-resistance of human ovarian cancer cells. J Ovarian Res. 2014 Aug 31;7:84. doi: 10.1186/s13048-014-0084-4.
• Ref 71: Effects of continuous exposure to digoxin on MDR1 function and expression in Caco-2 cells. J Pharm Pharmacol. 2003 May;55(5):675-81. doi: 10.1211/002235703765344595.
• Ref 72: [Effects of lncRNA RP11-770J1.3 and TMEM25 expression on paclitaxel resistance in human breast cancer cells]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2017 Jul 25;46(4):364-370. doi: 10.3785/j.issn.1008-9292.2017.08.04.
• Ref 73: LINC00473 promotes the Taxol resistance via miR-15a in colorectal cancer. Biosci Rep. 2018 Sep 20;38(5):BSR20180790. doi: 10.1042/BSR20180790. Print 2018 Oct 31.
• Ref 74: Perphenazine and prochlorperazine decrease glioblastoma U-87 MG cell migration and invasion: Analysis of the ABCB1 and ABCG2 transporters, E-cadherin, Alpha-tubulin and integrins (Alpha3, Alpha5, and Beta1) levels .Oncol Lett. 2022 Jun;23(6):182. doi: 10.3892/ol.2022.13302. Epub 2022 Apr 15. 10.3892/ol.2022.13302
• Ref 75: Mechanisms of drug resistance in status epilepticus .Epilepsia. 2007;48 Suppl 8:74-7. doi: 10.1111/j.1528-1167.2007.01357.x. 10.1111/j.1528-1167.2007.01357.x
• Ref 76: Multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: impact on susceptibility and response to steroids .Gene. 2013 Nov 10;530(2):201-7. doi: 10.1016/j.gene.2013.08.045. Epub 2013 Aug 27. 10.1016/j.gene.2013.08.045
• Ref 77: Effects of the multidrug resistance-1 gene on drug resistance in primary immune thrombocytopenia .Autoimmunity. 2016 Nov;49(7):486-495. doi: 10.1080/08916934.2016.1191476. Epub 2016 Jun 3. 10.1080/08916934.2016.1191476
• Ref 78: Multidrug resistance-1 (MDR-1) in autoimmune disorders IV. P-glycoprotein overfunction in lymphocytes from myasthenia gravis patients .Biomed Pharmacother. 2004 Jun;58(5):320-4. doi: 10.1016/j.biopha.2004.04.008. 10.1016/j.biopha.2004.04.008
• Ref 79: Verapamil and riluzole cocktail liposomes overcome pharmacoresistance by inhibiting P-glycoprotein in brain endothelial and astrocyte cells: A potent approach to treat amyotrophic lateral sclerosis .Eur J Pharm Sci. 2018 Jul 30;120:30-39. doi: 10.1016/j.ejps.2018.04.026. Epub 2018 Apr 26. 10.1016/j.ejps.2018.04.026
• Ref 80: The dual cyclooxygenase/5-lipoxygenase inhibitor licofelone attenuates p-glycoprotein-mediated drug resistance in the injured spinal cord .J Neurotrauma. 2013 Feb 1;30(3):211-26. doi: 10.1089/neu.2012.2587. Epub 2013 Jan 23. 10.1089/neu.2012.2587
• Ref 81: Association of ACE and MDR1 Gene Polymorphisms with Steroid Resistance in Children with Idiopathic Nephrotic Syndrome .Genet Test Mol Biomarkers. 2015 Aug;19(8):454-6. doi: 10.1089/gtmb.2015.0077. Epub 2015 Jul 8. 10.1089/gtmb.2015.0077
• Ref 82: Long non-coding RNA TUSC7 inhibits temozolomide resistance by targeting miR-10a in glioblastoma. Cancer Chemother Pharmacol. 2018 Apr;81(4):671-678. doi: 10.1007/s00280-018-3522-y. Epub 2018 Feb 3.
• Ref 83: Knockdown of long noncoding RNA H19 sensitizes human glioma cells to temozolomide therapy. Onco Targets Ther. 2016 Jun 13;9:3501-9. doi: 10.2147/OTT.S96278. eCollection 2016.
• Ref 84: A MDR1 (ABCB1) gene single nucleotide polymorphism predicts outcome of temozolomide treatment in glioblastoma patients. Ann Oncol. 2009 Jan;20(1):175-81. doi: 10.1093/annonc/mdn548. Epub 2008 Aug 7.
• Ref 85: Gamma-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the Gamma-Tocotrienol-NF-kB-P-gp axis .J Steroid Biochem Mol Biol. 2021 May;209:105835. doi: 10.1016/j.jsbmb.2021.105835. Epub 2021 Feb 5. 10.1016/j.jsbmb.2021.105835
• Ref 86: The phosphodiesterase-5 inhibitor vardenafil is a potent inhibitor of ABCB1/P-glycoprotein transporter .PLoS One. 2011 Apr 28;6(4):e19329. doi: 10.1371/journal.pone.0019329. 10.1371/journal.pone.0019329
• Ref 87: Enhanced expression of the multidrug resistance gene in vindesine-resistant human esophageal cancer cells .Oncology. 1994 Sep-Oct;51(5):440-5. doi: 10.1159/000227380. 10.1159/000227380
• Ref 88: Identifying a resistance determinant for the antimitotic natural products disorazole C1 and A1. J Pharmacol Exp Ther. 2010 Mar;332(3):906-11. doi: 10.1124/jpet.109.162842. Epub 2009 Dec 15.
• Ref 89: Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein .Pharmaceuticals (Basel). 2021 Dec 10;14(12):1292. doi: 10.3390/ph14121292. 10.3390/ph14121292