PCA3 Silencing Sensitizes Prostate Cancer Cells to Enzalutamide-mediated Androgen Receptor Blockade.
Anticancer Res
; 37(7): 3631-3637, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28668854
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.
Palabras clave
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Feniltiohidantoína
/
Receptores Androgénicos
/
Antagonistas de Receptores Androgénicos
/
Neoplasias de la Próstata Resistentes a la Castración
/
Antígenos de Neoplasias
Límite:
Humans
/
Male
Idioma:
En
Revista:
Anticancer Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Turquía
Pais de publicación:
Grecia