Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms
| Autor: | Skyler Kuhn, Michael M Gottesman, Frances Maher, Da Yin, Robert W. Robey, Jordan M. Hotz, Sachi Horibata, Ruchi P. Patel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Vincristine Original article Anti-microtubule drugs Combination therapy FTC fumitremorgin C TNF PBS phosphate-buffered saline Drug resistance Biology lcsh:RC254-282 MEM minimum essential medium 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine GTP guanosine triphosphate FBS fetal bovine serum GSEA gene set enrichment analysis Ovarian cancer medicine STR short tandem repeat Cisplatin TNF tumor necrosis factor VIN vincristine medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens SEM standard error of mean PTX paclitaxel 030104 developmental biology IMEM improved minimal essential medium Oncology Paclitaxel chemistry Cell culture 030220 oncology & carcinogenesis Cancer research COL colchicine Tumor necrosis factor alpha EMT epithelial-to-mesenchymal transition medicine.drug NFκB |
| Zdroj: | Translational Oncology Translational Oncology, Vol 14, Iss 1, Pp 100917-(2021) |
| ISSN: | 1936-5233 |
| Popis: | Highlights • Subpopulations of cisplatin-resistant cells are cross-resistant to anti-microtubule drugs. • Resistance mechanisms in cisplatin-resistant ovarian cancer cells are diverse. • Increased TNF and NFκB signaling found in cisplatin-resistant subpopulations treated with anti-microtubule drugs. 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/NFκB signaling, among other enriched pathways, suggesting that cross-resistance was due to more general survival mechanisms found in the cisplatin-selected cells. |
| Databáze: | OpenAIRE |
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