Niclosamide enhances abiraterone treatment via inhibition of androgen receptor variants in castration resistant prostate cancer

Chengfei Liu, Cameron Armstrong, Yezi Zhu, Wei Lou, Allen C Gao

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Considerable evidence from both clinical and experimental studies suggests that androgen receptor variants, particularly androgen receptor variant 7 (AR-V7), are critical in the induction of resistance to enzalutamide and abiraterone. In this study, we investigated the role of AR-V7 in the cross-resistance of enzalutamide and abiraterone and examined if inhibition of AR-V7 can improve abiraterone treatment response. We found that enzalutamide-resistant cells are cross-resistant to abiraterone, and that AR-V7 confers resistance to abiraterone. Knock down of AR-V7 by siRNA in abiraterone resistant CWR22Rv1 and C4-2B MDVR cells restored their sensitivity to abiraterone, indicating that AR-V7 is involved in abiraterone resistance. Abiraterone resistant prostate cancer cells generated by chronic treatment with abiraterone showed enhanced AR-V7 protein expression. Niclosamide, an FDAapproved antihelminthic drug that has been previously identified as a potent inhibitor of AR-V7, re-sensitizes resistant cells to abiraterone treatment in vitro and in vivo. In summary, this preclinical study suggests that overexpression of AR-V7 contributes to resistance to abiraterone, and supports the development of combination of abiraterone with niclosamide as a potential treatment for advanced castration resistant prostate cancer.

Original languageEnglish (US)
Pages (from-to)32210-32220
Number of pages11
JournalOncotarget
Volume7
Issue number22
DOIs
StatePublished - May 31 2016

Keywords

  • Abiraterone
  • Androgen receptor variant
  • Niclosamide
  • Prostate cancer
  • Resistance

ASJC Scopus subject areas

  • Oncology

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