Abstract
Several studies have shown that transient receptor potential cation channel subfamily M member 8 (TRPM8), which has been regarded as a novel prostate-specific marker, serves a key role in processes such as the proliferation, viability and cell migration of prostate cancer cells. Efforts have been made to uncover the potential role of targeting TRPM8 in the management of prostate cancer; it has been verified that TRPM8-targeted blockade, either by RNA interference-mediated depletion or specific TRPM8 inhibitors, could reduce the rate of proliferation and proliferative fraction, and induce apoptosis in prostate cancer cells. The aim of the present study was to investigate the effect of knockdown of TRPM8 on chemosensitivity in prostate cancer LNCaP and PC3 cells. The RNA interference-mediated depletion of TRPM8 inhibited proliferation and enhanced epirubicin chemosensitivity of LNCaP and PC3 cells, and promoted epirubicin-induced apoptosis by increasing the phosphorylation of p38 mitogen-activated protein kinase (hereafter p38) and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase signaling pathways, which was demonstrated via the use of specific inhibitors of phosphorylation of p38 and JNK. The results demonstrate that the targeted silencing of TRPM8 expression is a therapeutic strategy for treatment of prostate cancer that has considerable potential, even for castration-resistant prostate cancer.