The Role of 5αR Inhibitors in the Early Growth of Pca Cells

Abstract

Aim of this study is to investigate the efficacy of Finasteride (MK906), a selective 5α reductase type 2(5αR2) inhibitor, and of MK386, a selective 5α reductase type 1 (5αR1), on the cellular proliferation of primary cell cultures derived from patients with prostatic diseases.

Methods

We evaluated the effects of Finasteride and MK386 in 30 primary cultures obtained from prostatic carcinoma (PCa), 6 from high grade intraepithelial neoplasia (HGPIN) and 10 from benign prostatic hyperplasia (BPH).

Results

Primary cultures require testosterone (T) for optimal growth and both 5αR inhibitors decreased cell proliferation of primary cultures of PCa cells. IC50 values of Finasteride were lower when compared to those of MK386. In particular, Finasteride was more active in cultures derived from Gleason 2–6 PCa, compared to those derived from Gleason 7–10 PCa. On the contrary, we observed higher effectiveness of MK386 in Gleason 7–10 PCa derived cultures compared to those derived from Gleason 2–6 PCa tissues. The growth of PCa primary cultures was down-modulated by MK386 through a direct inhibition of the epithelial 5αR1, whereas the anti-proliferative activity of Finasteride seems to be mediated by stromal cells present in the primary cultures.

Conclusions

We found biological evidence for an important role of 5αR inhibitors in the early growth of PCa cells and for the necessity of combining anti-hormonal treatment for a sustained inhibition of PCa through the inhibition of stromal cell function even in advanced and androgen-resistant tumor progression phases.