Docetaxel-mediated autophagy promotes chemoresistance in castration-resistant prostate cancer cells by inhibiting STAT3

Cancer Lett. 2018 Mar 1:416:24-30. doi: 10.1016/j.canlet.2017.12.013. Epub 2017 Dec 13.

Abstract

Signal transducer and activator of transcription (STAT)3 expression is correlated with neoplasm growth, metastasis, and prognosis; it has also been implicated in the regulation of autophagy, which may in turn contribute to tumor chemoresistance. However, it is unknown whether STAT3 is involved in cancer cell survival in response to chemotherapy. In this study, we show that autophagy is triggered during chemotherapy and that inhibiting autophagy increased chemosensitivity of castration-resistant prostate cancer (CRPC) cells. Meanwhile, docetaxel induced autophagy was inhibited by STAT3 activation, which increased mitochondrial damage and decreased CRPC cell viability. These results suggest that STAT3 contributes to CRPC cell survival and chemoresistance by modulating autophagy.

Keywords: Autophagy; Castration-resistant prostate cancer; Chemotherapy; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Autophagy / drug effects*
  • Autophagy / genetics
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Docetaxel
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Prostatic Neoplasms, Castration-Resistant / genetics
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Taxoids / pharmacology*

Substances

  • Antineoplastic Agents
  • STAT3 Transcription Factor
  • Taxoids
  • Docetaxel