YM155 Reverses Cabazitaxel Resistance in Castration-resistant Prostate Cancer by Reducing Survivin Expression
YM155 Reverses Cabazitaxel Resistance in Castration-resistant Prostate Cancer by Reducing Survivin Expression
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DOI：
10.21873/anticanres.14512
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发表时间：
2020-09
影响因子：
2
通讯作者：
T. Miyao;H. Koike;Y. Sekine;Akira Ohtsu;D. Oka;Kazuhiro Suzuki
中科院分区：
文献类型：
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作者：
T. Miyao;H. Koike;Y. Sekine;Akira Ohtsu;D. Oka;Kazuhiro Suzuki
背景/目的：本研究的目的是阐明用YM 155（一种新型的生存素小分子抑制剂）治疗是否逆转去势抵抗性前列腺癌（CRPC）的卡巴他赛耐药性。材料和方法：在去势抵抗的前列腺癌细胞系22 Rv 1-CR中诱导卡巴他赛耐药性。使用体外和体内模型来测试YM 155和卡巴他赛的功效。结果：Survivin基因在22 Rv 1-CR细胞中的表达明显高于其亲本细胞（22 Rv 1）。在22 Rv 1-CR细胞中，YM 155以浓度依赖性方式显著降低存活素基因的表达。单独使用YM 155的效果较差;然而，它在体外和体内显著增强了卡巴他赛对22 Rv 1-CR的抗癌作用。结论：YM 155抑制survivin克服了CRPC细胞对卡巴他赛的耐药性。
Background/Aim: The purpose of the present study was to clarify whether treatment with YM155, a novel small-molecule inhibitor of survivin, reversed cabazitaxel resistance in castration-resistant prostate cancer (CRPC). Materials and Methods: Cabazitaxel resistance was induced in the castration-resistant prostate cancer cell line, 22Rv1-CR. In vitro and in vivo models were used to test the efficacy of YM155 and cabazitaxel. Results: Survivin gene expression was significantly higher in 22Rv1-CR than its parent cells (22Rv1). In 22Rv1-CR cells, YM155 significantly reduced expression of the survivin gene in a concentration-dependent manner. YM155 alone was poorly effective; however, it significantly enhanced the anticancer effects of cabazitaxel on 22Rv1-CR in vitro and in vivo. Conclusion: Inhibition of survivin by YM155 overcomes cabazitaxel resistance in CRPC cells.