5α‐reductase inhibition to decrease prostate tumor growth

Abstract

5α-reductase 1 (5αR1) and 5α-reductase 2 (5αR2) convert testosterone into the more potent androgen dihydrotestosterone (DHT). We hypothesized that finasteride (5αR2 inhibitor) treatment pre (1–2 weeks before) or post (3 weeks after) tumor implantation would not significantly alter tumor growth because of the presence of 5αR1, while dutasteride (5αR1 & 2 dual inhibitor) treatment would decrease tumor growth regardless of when treatment began. Sixty 8-week old male nude mice were randomized into Control, Pre & Post-Finasteride, Pre & Post-Dutasteride diet groups (all diets contained 83.3 mg drug/kg diet). Tumors were implanted by subcutaneous injection of 1 × 105 WPE1-NA22 human prostate cancer cells in Matrigel. All treatment groups had significantly decreased prostate and seminal vesicle weights versus the control. Dutasteride intake also significantly reduced seminal vesicle weights compared to finasteride intake. There were no significant differences in final tumor areas and tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 cells, and its parent line RWPE-1 prostate epithelial cells were not altered by treatment with testosterone, DHT, or mibolerone suggesting that they may not be androgen-sensitive. Thus, the lack of androgen-responsiveness of WPE-1-NA22 may explain the inadequate tumor growth observed. (NIH Grant P20-RR017686)