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

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

ANTICANCER RESEARCH, cilt.37, sa.7, ss.3631-3637, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 37 Sayı: 7
  • Basım Tarihi: 2017
  • Doi Numarası: 10.21873/anticanres.11733
  • Dergi Adı: ANTICANCER RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.3631-3637
  • Anahtar Kelimeler: Prostate cancer, PCA3, enzalutamide, androgen receptor, MECHANISMS, EXPRESSION, RNA, PCGEM1, AXIS, GENE
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.