YM155 enhances docetaxel efficacy in ovarian cancer
YM155 enhances docetaxel efficacy in ovarian cancer
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YM155 增强多西紫杉醇治疗卵巢癌的疗效
DOI：
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发表时间：
2018
影响因子：
2.2
通讯作者：
Xiao-Jian Yan
中科院分区：
文献类型：
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作者：
Li-Jiao Hou;Xiao-Xiu Huang;Li-Na Xu;Yan-Yan Zhang;Na Zhao;Rong-Ying Ou;Wen-Feng Li;Wen-Ji Zhang;Qi-Wei Jiang;Yang Yang;Meng-Ning Wei;Jia-Rong Huang;Kun Wang;Meng-Ling Yuan;Zi-Hao Xing;Zhi Shi;Xiao-Jian Yan
YM155（Sepantronium bromide）是一种有效的生存素小分子抑制剂，通过抑制生存素表达，在多种癌症中显示出有前景的抗癌活性。多西他赛（Taxotere®）是紫杉烷类药物中的一员，在临床上用于治疗多种癌症。尽管多西紫杉醇的治疗效果令人鼓舞，但新出现的耐药性是一个紧迫的问题。在本研究中，我们研究了 YM155 对卵巢癌细胞中多西紫杉醇疗效的影响。我们的数据表明，YM155 通过下调卵巢癌细胞中的生存素来主动诱导细胞生长抑制、细胞周期停滞和细胞凋亡。此外，YM155 增加了细胞内 ROS 水平，并且用 NAC 或 GSH 预处理仅在亲代 A2780 细胞中部分逆转了 YM155 诱导的 ROS 积累和细胞凋亡，但在耐药 A2780/Taxol 细胞中则不然。此外，YM155 增强了多西紫杉醇抑制卵巢癌细胞生长并诱导细胞凋亡的功效。综上所述，我们的结果表明，YM155 和多西紫杉醇的组合可能是治疗卵巢癌的可行策略。
YM155 (Sepantronium bromide) is a potent small molecule inhibitor of survivin by suppression of survivin expression and shows the promising anticancer activity in many types of cancers. Docetaxel (Taxotere®) is a member of the taxane drugs used in the treatment of a number of cancers in clinic. Despite the therapeutic efficacy of docetaxel is encouraging, the emergent resistance is an urgent issue. In this study, we investigate the effect of YM155 on docetaxel efficacy in ovarian cancer cells. Our data showed that YM155 actively induced cell growth inhibition, cell cycle arrest and apoptosis with downregualtion of survivin in ovarian cancer cells. Moreover, YM155 increased the intracellular ROS levels, and pretreatment with either NAC or GSH partially reversed the YM155-induced ROS accumulation and apoptosis only in the parental A2780 cells, but not in the resistant A2780/Taxol cells. Furthermore, YM155 enhanced docetaxel efficacy to inhibit the growth and induce apoptosis in ovarian cancer cells. Take together, our results suggested that combination of YM155 and docetaxel may be a feasible strategy for the treatment of ovarian cancer.