YM155 Reverses Cabazitaxel Resistance in Castration-resistant Prostate Cancer by Reducing Survivin Expression

Abstract

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.

Keywords: Castration-resistant prostate cancer; YM155; cabazitaxel; drug therapy; inhibitor of apoptosis proteins; survivin.