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Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms.

ABSTRACT: Although the first line of therapy for epithelial ovarian cancer typically consists of taxane-platinum combination therapy, many patients develop a platinum-resistant tumor within a year. Several previous studies have looked at this cross-resistance between cisplatin and anti-microtubule drugs, but their findings have been somewhat conflicting. Here, we developed cisplatin-resistant cell lines that are resistant to low and high levels of cisplatin and explored the effects of three anti-microtubule drugs (paclitaxel, vincristine, and colchicine) on the parental and cisplatin-resistant cells. We found that cells resistant to lower levels of cisplatin were no more resistant to anti-microtubule drugs than parental cells, while cells that were resistant to higher levels of cisplatin had a subpopulation of cells that were cross-resistant to anti-microtubule drugs, clarifying discrepancies within the field. We then isolated this subpopulation by applying selective pressure with anti-microtubule drugs and performed RNA sequencing and gene set enrichment analysis to identify resistance mechanisms. This subpopulation was found to express increased levels of pro-survival TNF/NF?B signaling, among other enriched pathways, suggesting that cross-resistance was due to more general survival mechanisms found in the cisplatin-selected cells.

SUBMITTER: Patel RP

PROVIDER: S-EPMC7586247 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms.

Patel Ruchi P RP Kuhn Skyler S Yin Da D Hotz Jordan M JM Maher Frances A FA Robey Robert W RW Gottesman Michael M MM Horibata Sachi S

Translational oncology 20201022 1

Although the first line of therapy for epithelial ovarian cancer typically consists of taxane-platinum combination therapy, many patients develop a platinum-resistant tumor within a year. Several previous studies have looked at this cross-resistance between cisplatin and anti-microtubule drugs, but their findings have been somewhat conflicting. Here, we developed cisplatin-resistant cell lines that are resistant to low and high levels of cisplatin and explored the effects of three anti-microtubu ...[more]

PMID: 33129114

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Dataset Information

Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms.

Publications

Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms.

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