Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms.
Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms.
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DOI：
10.1016/j.tranon.2020.100917
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发表时间：
2021-01
影响因子：
5
通讯作者：
Horibata S
中科院分区：
文献类型：
--
作者：
Patel RP;Kuhn S;Yin D;Hotz JM;Maher FA;Robey RW;Gottesman MM;Horibata S
顺铂耐药细胞亚群对抗微管药物具有交叉耐药性。顺铂耐药的卵巢癌细胞的耐药机制是多种多样的。在接受抗微管药物治疗的顺铂耐药亚群中发现 TNF 和 NFκB 信号传导增强。尽管上皮性卵巢癌的一线治疗通常包括紫杉烷-铂联合治疗，但许多患者在一年内出现铂耐药肿瘤。之前的几项研究已经研究了顺铂和抗微管药物之间的交叉耐药性，但他们的发现有些相互矛盾。在这里，我们开发了对低水平和高水平顺铂具有耐药性的顺铂耐药细胞系，并探讨了三种抗微管药物（紫杉醇、长春新碱和秋水仙碱）对亲本细胞和顺铂耐药细胞的影响。我们发现，对较低水平顺铂耐药的细胞对抗微管药物的耐药性并不比亲本细胞更强，而对较高水平顺铂耐药的细胞则有一个细胞亚群对抗微管药物具有交叉耐药性，这澄清了该领域内的差异。然后，我们通过使用抗微管药物施加选择性压力来分离该亚群，并进行 RNA 测序和基因集富集分析，以确定耐药机制。发现该亚群表达增加水平的促生存 TNF/NFκB 信号传导以及其他丰富的途径，表明交叉耐药性是由于在顺铂选择的细胞中发现的更普遍的生存机制所致。
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.
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影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
通过维持一定数量的顺铂敏感细胞来延缓顺铂耐药性发展的策略
影响因子：
4.6
作者：
Duan G;Tang Q;Yan H;Xie L;Wang Y;Zheng XE;Zhuge Y;Shen S;Zhang B;Zhang X;Wang J;Wang W;Zou X
通讯作者：
Zou X
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
14.9
作者：
Kim S;Chen J;Cheng T;Gindulyte A;He J;He S;Li Q;Shoemaker BA;Thiessen PA;Yu B;Zaslavsky L;Zhang J;Bolton EE
通讯作者：
Bolton EE
影响因子：
6.4
作者：
Hubaux R;Thu KL;Vucic EA;Pikor LA;Kung SH;Martinez VD;Mosslemi M;Becker-Santos DD;Gazdar AF;Lam S;Lam WL
通讯作者：
Lam WL