Tumor necrosis factor-α-induced a disintegrin and metalloprotease 10 increases apoptosis resistance in prostate cancer cells

Abstract

In developed countries, prostate cancer (PCa) is the second most frequently diagnosed type of cancer and the third most common cause of cancer-related mortality in males. Compared with western countries, the morbidity rate of PCa in China is markedly lower, however, it is rising annually. The etiology of PCa is unclear, therefore, to investigate how a disintegrin and metalloprotease 10 (ADAM10) functions in PCa, ADAM10 mRNA and protein levels induced by tumor necrosis factor (TNF)-α were identified using polymerase chain reaction and flow cytometry, respectively. To investigate the mechanism of ADAM10 activity in PCa, specific inhibitors were used, and DNA transfection and RNA interference technology were employed to identify the interaction between ADAM10 and the Fas ligand (L). The results indicated that TNF-α induced ADAM10 expression in a time- and dose-dependent manner through the p38 mitogen-activated protein kinase/necrosis factor-κB signaling pathway. ADAM10 hydrolyzed FasL and contributed to apoptosis resistance of the tumor cells. These observations indicate a promising therapeutic modality for the treatment of apoptosis-resistant PCa, by targeting ADAM10 sheddase activity.