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.
Keywords: Ovarian cancer; YM155; docetaxel.