Cross-resistance of cisplatin selected cells to anti-microtubule agents : Role of general survival mechanisms
Published by Elsevier Inc..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Translational oncology - 14(2021), 1 vom: 15. Jan., Seite 100917 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Patel, Ruchi P [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-microtubule drugs |
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| Anmerkungen: |
Date Revised 10.01.2021 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.tranon.2020.100917 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316975664 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Published by Elsevier Inc. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anti-microtubule drugs | |
| 650 | 4 | |a Cisplatin | |
| 650 | 4 | |a Drug resistance | |
| 650 | 4 | |a NFκB | |
| 650 | 4 | |a Ovarian cancer | |
| 650 | 4 | |a TNF | |
| 700 | 1 | |a Kuhn, Skyler |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Da |e verfasserin |4 aut | |
| 700 | 1 | |a Hotz, Jordan M |e verfasserin |4 aut | |
| 700 | 1 | |a Maher, Frances A |e verfasserin |4 aut | |
| 700 | 1 | |a Robey, Robert W |e verfasserin |4 aut | |
| 700 | 1 | |a Gottesman, Michael M |e verfasserin |4 aut | |
| 700 | 1 | |a Horibata, Sachi |e verfasserin |4 aut | |
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