title: Reduced accumulation of platinum drugs is not observed in drug-resistant ovarian cancer cell lines derived from cisplatin-treated patients.
abstract: The resistance of ovarian cancer towards front-line chemotherapy, usually cisplatin or carboplatin in combination with paclitaxel or docetaxel, remains a major clinical challenge. Resistance to these agents has been largely studied using cell lines selected for resistance to agents in vitro. We examined a series of paired cell lines derived from patients with ovarian cancer prior to chemotherapy (PEO1, PEO4, PEO14 and PEA1), and following the acquisition of resistance to a platinum-based chemotherapy regimen (PEO6, PEO23 and PEA2, respectively). All resistant patient lines showed resistance to cisplatin (2-5-fold), but this did not correspond with lowered accumulation. No general cross-resistance was observed for oxaliplatin, paclitaxel or docetaxel, and paclitaxel accumulation was not affected. PEO1 cells carrying BRCA2 mutations were hypersensitive to the PARP inhibitors olaparib and velaparib, but all other cell lines expressing functional forms of BRCA2 were less sensitive. While reduced drug accumulation was not observed, we believe these pairs of lines are of use to researchers studying Pt drug resistance and experimental therapeutics against drug-resistant ovarian cancer.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Marina
authors.initials: M
authors.lastname: Stukova
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hall
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Samantha D
authors.initials: SD
authors.lastname: Tsotsoros
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
authors.forename: James P
authors.initials: JP
authors.lastname: Madigan
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Farrell
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States. Electronic address: mgottesman@nih.gov.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gottesman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D024522:Genes, BRCA2; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D002945:Cisplatin
keywords: Drug resistance; Mechanism; Metals in medicine; Ovarian cancer