Drug Information

Drug (ID: DG01814) and It's Reported Resistant Information

• Name: Cisplatinum
• Synonyms: Cis-Platin; cis-DDP; Cisplatine; Cisplatino; Cisplatinum; Lederplatin; Briplatin; Cismaplat; Neoplatin; Platamine; Platinex; Randa; trans-platin; cis-Dichlorodiammineplatinum(II); Peyrone's salt; cis-Diamminedichloroplatinum; Peyrone's chloride; trans-Platinum(II) ammonium chloride; cis-[PtCl2(NH3)2]; trans-Dichlorodiammine platinum; trans-Platinumdiammine dichloride; CHEBI:27899; CHEBI:35852; TRANS-DIAMMINEDICHLOROPLATINUM; trans-Platinum(II) diamminedichloride; trans-DDP, 8; Cisplatin, 1; Epitope ID:194799; Epitope ID:194800; BDBM92386; cis-diamminedichloridoplatinum(II); (SP-4-1)-diamminedichloroplatinum; (SP-4-2)-diamminedichloroplatinum; trans-diamminedichloridoplatinum(II); (SP-4-1)-diamminedichloridoplatinum; (SP-4-2)-diamminedichloridoplatinum; AKOS025117566; DB00515; EU-0100918
• Indication:
  In total 2 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
  Osteosarcoma [ICD-11: 2B51]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (7 diseases)
  Brain cancer [ICD-11: 2A00]; [2]
  Colorectal cancer [ICD-11: 2B91]; [1]
  Liver cancer [ICD-11: 2C12]; [3]
  Lung cancer [ICD-11: 2C25]; [4]
  Melanoma [ICD-11: 2C30]; [5]
  Nasopharyngeal cancer [ICD-11: 2B6B]; [6]
  Pancreatic cancer [ICD-11: 2C10]; [7]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [8]
  Lung cancer [ICD-11: 2C25]; [9]
• Target: Human Deoxyribonucleic acid (hDNA); NOUNIPROTAC; [1]
• IsoSMILES: N.N.Cl[Pt+2]Cl
• InChI: InChI=1S/2ClH.2H3N.Pt/h2*1H;2*1H3;/q;;;;+4/p-2
• InChIKey: BSJGASKRWFKGMV-UHFFFAOYSA-L
• PubChem CID: 441203
• VARIDT ID: DR0332
• INTEDE ID: DR00291
• DrugBank ID: DB12117

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOXD antisense growth-associated long non-coding RNA (HAGLR) [2]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Brain glioma [ICD-11: 2A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: SNB19 cells; Brain; Homo sapiens (Human); CVCL_0535
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: NHA cells; Brain; Homo sapiens (Human); N.A.
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Knockdown of LncRNA HOXD-AS1 suppresses proliferation, migration and invasion and enhances cisplatin sensitivity of glioma cells by sponging miR-204.

Nasopharyngeal cancer [ICD-11: 2B6B]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Deleted in lymphocytic leukemia 1 (DLEU1) [6]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 5-8F cells; Nasopharynx; Homo sapiens (Human); CVCL_C528
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: C666-1 cells; Throat; Homo sapiens (Human); CVCL_7949
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vitro Model: 6-10B cells; Nasopharynx; Homo sapiens (Human); CVCL_C529
• In Vitro Model: SUNE-1 cells; Nasopharynx; Homo sapiens (Human); CVCL_6946
• In Vitro Model: HONE-1 cells; Nasopharynx; Homo sapiens (Human); CVCL_8706
• In Vitro Model: HNE-1 cells; Nasopharynx; Homo sapiens (Human); CVCL_0308
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Microarray assay; Luciferase assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: DLEU1 acts as an oncogene to promote DDP resistance and BIRC6 expression in NPC through interacting with miR-381-3p, which may help to develop new strategy against NPC chemoresistance.

Colorectal cancer [ICD-11: 2B91]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (CRCAL-3) [1]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• 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 Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Knockdown assay
• Experiment for Drug Resistance: Crystal violet assay
• Mechanism Description: CRCAL-3 knockdown was observed in xenograft models to repress cell proliferation and enhance cisplatin sensitivity.

Pancreatic cancer [ICD-11: 2C10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: MACC1 antisense RNA 1 (MACC1-AS1) [7]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PAX8/NOTCH1 signaling pathway; Activation; hsa04330
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: AsPC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• In Vitro Model: KP-2 cells; Pancreas; Homo sapiens (Human); CVCL_3004
• In Vivo Model: Male BALB/c nude mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: Microarray assay; qRT-PCR; Western bloting analysis; Luciferase assay; RIP experiments assay; RNA pull down assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Long non-coding RNA MACC1-AS1 promoted pancreatic carcinoma progression through activation of PAX8/NOTCH1 signaling pathway.

Liver cancer [ICD-11: 2C12]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Cancer susceptibility 2 (CASC2) [3]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Huh7 cells; Kidney; Homo sapiens (Human); CVCL_U442
• In Vitro Model: SMMC-7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• Experiment for Molecule Alteration: Overexpression assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of CASC2 Improves Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222.

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Urothelial cancer associated 1 (UCA1) [9]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Knockdown assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Compared with the A549 group, the expressions of N-cadherin, vimentin, and Snail was significantly upregulated in A549/DDP group, but E-cadherin was significantly downregulated.Compared with the shCon group, the abundance of N-cadherin, vimentin, and Snail was significantly downregulated in short hairpin RNA UCA1 (shUCA1) group, while E-cadherin was significantly upregulated.

Key Molecule: Taurine up-regulated 1 (TUG1) [4]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SPC-A1 cells; Lung; Homo sapiens (Human); CVCL_6955
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Overexpression assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: TUG1 overexpression was shown to inhibit cell proliferation, migration, invasion, but facilitate apoptosis and autophagy in NSCLC cells resistant to cisplatin (DDP).

Key Molecule: Long non-protein coding RNA 707 (LINC00707) [10]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Luciferase assay; Knockdown assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Silencing long intergenic non-coding RNA 00707 enhances cisplatin sensitivity in cisplatin-resistant non-small-cell lung cancer cells by sponging miR-145.

Key Molecule: Long non-protein coding RNA 221 (LINC00221) [11]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Sk-MES-1 cells; Lung; Homo sapiens (Human); CVCL_0630
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western bloting analysis; qRT-PCR; Dual luciferase assay; Pull down experiments assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Linc00221 promotes cisplatin resistance in NSCLC through the downstream miR-519a/ZBTB5 signaling axis, which could be used as a potential diagnostic and therapeutic target for clinical cisplatin-resistant NSCLC patients.

Key Molecule: HOX transcript antisense RNA (HOTAIR) [12]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Wnt signaling pathway; Inhibition; hsa04310
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Knockdown assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The action mechanism of LncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway.

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: H19, imprinted maternally expressed transcript (H19) [5]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: M8 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: WM35 cells; Skin; Homo sapiens (Human); CVCL_0580
• In Vitro Model: SK-MEL-2 cells; Skin; Homo sapiens (Human); CVCL_0069
• In Vitro Model: A2508 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Knockdown assay; qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of LncRNA H19 sensitizes melanoma cells to cisplatin by regulating the miR-18b/IGF1 axis.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HLA complex P5 (HCP5) [8]

• Molecule Alteration: Down-regulation; Expression
• Resistant Disease: Triple negative breast cancer [ICD-11: 2C60.9]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231; Pleural effusion; Homo sapiens (Human); CVCL_0062
• In Vivo Model: BALB/c nude mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: Microarray assay; Western bloting analysis; Overexpression assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The downregulation of HCP5 contributed to DDP resistance in TNBC, while overexpression of HCP5 reversed the resistance via upregulating PTEN level.

References

• Ref 1: The expression of long noncoding RNA CRCAL-3 in colorectal cancer and its impacts on cell proliferation and migrationJ Cell Biochem. 2019 Sep;120(9):15369-15377. doi: 10.1002/jcb.28804. Epub 2019 Apr 30.
• Ref 2: Knockdown of lncRNA HOXD-AS1 suppresses proliferation, migration and invasion and enhances cisplatin sensitivity of glioma cells by sponging miR-204. Biomed Pharmacother. 2019 Apr;112:108633. doi: 10.1016/j.biopha.2019.108633. Epub 2019 Feb 20.
• Ref 3: Overexpression of CASC2 Improves Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222DNA Cell Biol. 2019 Nov;38(11):1366-1373. doi: 10.1089/dna.2019.4882. Epub 2019 Oct 18.
• Ref 4: Long non-coding RNA TUG1 enhances chemosensitivity in non-small cell lung cancer by impairing microRNA-221-dependent PTEN inhibitionAging (Albany NY). 2019 Sep 18;11(18):7553-7569. doi: 10.18632/aging.102271. Epub 2019 Sep 18.
• Ref 5: Downregulation of lncRNA H19 sensitizes melanoma cells to cisplatin by regulating the miR-18b/IGF1 axisAnticancer Drugs. 2020 Jun;31(5):473-482. doi: 10.1097/CAD.0000000000000888.
• Ref 6: Long Non-Coding RNA DLEU1 Up-Regulates BIRC6 Expression by Competitively Sponging miR-381-3p to Promote Cisplatin Resistance in Nasopharyngeal CarcinomaOnco Targets Ther. 2020 Mar 9;13:2037-2045. doi: 10.2147/OTT.S237456. eCollection 2020.
• Ref 7: Long non-coding RNA MACC1-AS1 promoted pancreatic carcinoma progression through activation of PAX8/NOTCH1 signaling pathwayJ Exp Clin Cancer Res. 2019 Aug 7;38(1):344. doi: 10.1186/s13046-019-1332-7.
• Ref 8: Long noncoding RNA HCP5 contributes to cisplatin resistance in human triple-negative breast cancer via regulation of PTEN expressionBiomed Pharmacother. 2019 Jul;115:108869. doi: 10.1016/j.biopha.2019.108869. Epub 2019 Apr 24.
• Ref 9: Silence of lncRNA UCA1 rescues drug resistance of cisplatin to non-small-cell lung cancer cells. J Cell Biochem. 2019 Jun;120(6):9243-9249. doi: 10.1002/jcb.28200. Epub 2019 Jan 16.
• Ref 10: Silencing long intergenic non-coding RNA 00707 enhances cisplatin sensitivity in cisplatin-resistant non-small-cell lung cancer cells by sponging miR-145Oncol Lett. 2019 Dec;18(6):6261-6268. doi: 10.3892/ol.2019.10959. Epub 2019 Oct 3.
• Ref 11: Linc00221 modulates cisplatin resistance in non-small-cell lung cancer via sponging miR-519aBiochimie. 2019 Jul;162:134-143. doi: 10.1016/j.biochi.2019.04.019. Epub 2019 Apr 25.
• Ref 12: A Compound AC1Q3QWB Selectively Disrupts HOTAIR-Mediated Recruitment of PRC2 and Enhances Cancer Therapy of DZNepTheranostics. 2019 Jun 24;9(16):4608-4623. doi: 10.7150/thno.35188. eCollection 2019.