Lovastatin Causes Diminished PSA Secretion by Inhibiting AR Expression and Function in LNCaP Prostate Cancer Cells

OBJECTIVES To investigate why statin users display a noticeable decline in prostate specific antigen (PSA) as revealed in recent clinical trials, we tested the effects of lovastatin on the androgen signaling cascade in lymph node carcinoma of the prostate (LNCaP) prostate cancer cells. METHODS Effects of lovastatin alone or in combination with a small interference RNA to inhibit AR expression on cell proliferation and induction of apoptosis were assessed by [H-3] thymidine incorporation and caspase-3 activity assay. PSA levels were measured in the cell culture supernatant by immunoassay. In addition, expression and activity of AR and Akt/protein kinase B (Akt) were determined by Western blotting and real-time polymerase chain reaction as well as by luciferase reporter gene assay. RESULTS Our results show that lovastatin significantly reduces AR expression and activity, resulting in decreased PSA levels. These effects were associated with inhibition of cell proliferation and induction of apoptosis. In addition, we observed that the Akt signaling pathway plays a pivotal role in lovastatin-mediated regulation of AR signaling. CONCLUSIONS Our data suggest that the regular use of statins may have beneficial effects in statin users by preventing prostate cancer growth through inhibition of androgen activation and expression, resulting in diminished PSA levels. UROLOGY 77: 1508.e1-1508.e7, 2011. (C) 2011 Elsevier Inc.