Effects of platelet-activating factor and its differential regulation by androgens and steroid hormones in prostate cancers.

Platelet-activating factor (PAF) is an arachidonic acid metabolite that plays an important role in cell proliferation, migration and neoangiogenesis, but whether it is involved in the progression of prostate cancer remains undiscovered. Clinical prostate specimens were investigated with immunohistochemistry method and in vitro cell experiments referred to MTS cell proliferation assay, invasion and migration experiment, quantitative real-time RT-PCR assay, western blotting analysis and ELISA assay. Platelet-activating factor synthetase, lyso-PAF acetyl transferase (LPCAT1), increased significantly in castration-resistant prostate cancer (CRPC) specimens and CRPC PC-3 cells than that in controls. Intriguingly, PAF induced invasion and migration of PC-3 cells but not LNCaP cells. The PAF receptor antagonist inhibited proliferation of LNCaP and PC-3 cells. Dihydrotestosterone (DHT) treatment caused a decrease in LPCAT1 expression and PAF release in LNCaP cells, which could be blocked by androgen receptor antagonists. Finally, DHT increased LPCAT1 expression and PAF release in PC-3 cells in a Wnt/β-catenin-dependent manner. For the first time, our data supported that PAF might play pivotal roles in the progression of prostate cancer, which might throw a new light on the treatment of prostate cancer and the prevention of the emergence of CRPC.