PCA3 Silencing Sensitizes Prostate Cancer Cells to Enzalutamide-mediated Androgen Receptor Blockade


Ozgur E., Celik A. I. , Darendeliler E., Gezer U.

ANTICANCER RESEARCH, vol.37, no.7, pp.3631-3637, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 7
  • Publication Date: 2017
  • Doi Number: 10.21873/anticanres.11733
  • Journal Name: ANTICANCER RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3631-3637
  • Keywords: Prostate cancer, PCA3, enzalutamide, androgen receptor, MECHANISMS, EXPRESSION, RNA, PCGEM1, AXIS, GENE
  • Istanbul University Affiliated: Yes

Abstract

Background/Aim: Prostate cancer (PCa) is an androgen-dependent disease. Novel anti-androgens (i.e. enzalutamide) have recently been developed for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Evidence is accumulating that prostate cancer antigen 3 (PCA3) is involved in androgen receptor (AR) signaling. Here, in combination with enzalutamide-mediated AR blockade, we investigated the effect of PCA3 targeting on the viability of PCa cells. Materials and Methods: In hormone-sensitive LNCaP cells, AR-overexpressing LNCaP-AR(+) cells and VCaP cells (representing CRPC), PCA3 was silenced using siRNA oligonucleotides. Gene expression and cell viability was assessed in PCA3-silenced and/or AR-blocked cells. Results: PCA3 targeting reduced the expression of AR-related genes (i.e. prostate-specific antigen (PSA) and prostate-specific transcript 1 (non-protein coding) (PCGEM1)) and potentiated the effect of enzalutamide. Proliferation of PCa cells was suppressed upon PCA3 silencing with a greater effect in LNCaP-AR(+) cells. Furthermore, PCA3 silencing sensitized PCa cells to enzalutamide-induced loss of cell growth. Conclusion: PCA3, as a therapeutic target in PCa, might be used to potentiate AR antagonists.