The impact of finasteride and dutasteride treatments on proliferation, apoptosis, androgen receptor, 5?-reductase 1 and 5?-reductase 2 in TRAMP mouse prostates.

ABSTRACT:

Background

Previously, we studied the effect of finasteride- or dutasteride-containing diets in male C57BL/6 TRAMP x FVB mice. Pre (6 weeks of age) and post (12 weeks of age) groups received finasteride or dutasteride to determine the efficacy of these pharmaceuticals on prostate cancer (PCa) development in male C57BL/6 TRAMP x FVB mice. Post-Dutasteride treatment was more effective than Pre-Dutasteride treatment, and dutasteride treatments were more effective than finasteride treatments in decreasing prostatic intraepithelial neoplasia (PIN) progression and PCa development. Finasteride and Pre-Dutasteride treatments significantly decreased high-grade PIN incidence, but increased poorly differentiated PCa incidence. In this study, molecular changes in prostates of these mice were characterized in an effort to elucidate the discordant response in Pre-Dutasteride and finasteride groups, and determine why Post-Dutasteride treatment was more effective.

Method/principal findings

Ki-67 (proliferation marker) and androgen receptor (AR) protein, apoptotic DNA fragmentation (TUNEL assay), 5?-reductase 1 (5?R1) and 5?-reductase 2 (5?R2) mRNA were quantified in male TRAMP mice prostate tissues with genitourinary weight < 1 and > 1 gram. Overall, proliferation and AR were decreased and apoptosis was increased in most tumors versus prostate epithelium and hyperplasia. Proliferation and AR were increased notably in hyperplasia versus prostate epithelium and tumor. There were no clear trends or differences in 5?-reductase 1 and 5?-reductase 2 levels between large and small tumors. The discordant response in Pre-Finasteride and Pre-Dutasteride groups may be due to upregulated 5?R1 levels in large versus small tumors. It is not clear what the mechanism is for the different response in the Post-Finasteride group. Post-Dutasteride treatment was more effective than Pre-Dutasteride treatment in decreasing 5?R1 in large tumors. Therefore, this may be why this treatment was more effective in decreasing PIN progression and PCa development.

Conclusion

The effect of finasteride and dutasteride on these biomarkers did not clearly elucidate their mechanism of action, but tumor 5?R1 levels were significantly positively correlated with adjusted prostate severe lesion score.

SUBMITTER: Opoku-Acheampong AB 

PROVIDER: S-EPMC5526468 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature