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 (8 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]
  Oral squamous cell carcinoma [ICD-11: 2B6E]; [7]
  Pancreatic cancer [ICD-11: 2C10]; [8]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [9]
  Lung cancer [ICD-11: 2C25]; [10]
• 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

  MRAP: Metabolic Reprogramming via Altered Pathways

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]

• Resistant Disease: Brain glioma [ICD-11: 2A00.0]
• Molecule Alteration: Up-regulation; Interaction
• 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]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Up-regulation; Interaction
• 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.

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [7]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

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]

• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Up-regulation; Expression
• 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) [8]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Up-regulation; Expression
• 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]

• Resistant Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Molecule Alteration: Down-regulation; Interaction
• 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) [10]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Up-regulation; Expression
• 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]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Down-regulation; Interaction
• 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) [11]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Up-regulation; Interaction
• 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) [12]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Up-regulation; Interaction
• 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) [13]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Up-regulation; Expression
• 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]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Up-regulation; Interaction
• 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.; 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) [9]

• Resistant Disease: Triple negative breast cancer [ICD-11: 2C60.1]
• Molecule Alteration: Down-regulation; Expression
• 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: Histone Lysine Lactylation (Kla)-induced BCAM Promotes OSCC Progression and Cis-Platinum Resistance. Oral Dis. 2025 Apr;31(4):1116-1132.
• Ref 8: 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 9: 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 10: 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 11: 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 12: 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 13: 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.