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

Anticancer Res. 2020 Sep;40(9):5091-5095. doi: 10.21873/anticanres.14512.

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.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Drug Resistance, Neoplasm / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Imidazoles / pharmacology*
  • Male
  • Mice
  • Naphthoquinones / pharmacology*
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • RNA, Messenger / genetics
  • Survivin / genetics*
  • Taxoids / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • BIRC5 protein, human
  • Imidazoles
  • Naphthoquinones
  • RNA, Messenger
  • Survivin
  • Taxoids
  • cabazitaxel
  • sepantronium