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PCA3 Silencing Sensitizes Prostate Cancer Cells to Enzalutamide-mediated Androgen Receptor Blockade.
- Source :
-
Anticancer research [Anticancer Res] 2017 Jul; Vol. 37 (7), pp. 3631-3637. - Publication Year :
- 2017
-
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.<br />Materials and Methods: In hormone-sensitive LNCaP cells, AR-overexpressing LNCaP-AR <superscript>+</superscript> 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.<br />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 <superscript>+</superscript> cells. Furthermore, PCA3 silencing sensitized PCa cells to enzalutamide-induced loss of cell growth.<br />Conclusion: PCA3, as a therapeutic target in PCa, might be used to potentiate AR antagonists.<br /> (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Subjects :
- Benzamides
Cell Line, Tumor
Cell Proliferation genetics
Cell Survival genetics
Gene Expression genetics
Gene Silencing physiology
Humans
Male
Nitriles
Phenylthiohydantoin pharmacology
Prostate metabolism
Prostate-Specific Antigen genetics
Prostatic Neoplasms, Castration-Resistant genetics
Prostatic Neoplasms, Castration-Resistant metabolism
Androgen Receptor Antagonists pharmacology
Antigens, Neoplasm genetics
Phenylthiohydantoin analogs & derivatives
Prostatic Neoplasms, Castration-Resistant drug therapy
Receptors, Androgen genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-7530
- Volume :
- 37
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 28668854
- Full Text :
- https://doi.org/10.21873/anticanres.11733