Exogenous WWOX enhances apoptosis and weakens metastasis in CNE2 nasopharyngeal carcinoma cells through the intrinsic apoptotic pathway

摘要

The WW domain containing oxidoreductase (WWOX) has been postulated to behave as a putative tumor suppressor and that silencing of WWOX expression is linked to the carcinogenesis and progression of various carcinomas. The role of WWOX in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we sought to evaluate the biological feature of WWOX restoration in human CNE2 NPC cells. In vitro experiments manifested that transiently overexpressed WWOX significantly suppressed proliferation as well as invasion and migration of the CNE2 cells. Of note, WWOX-induced apoptosis could be partly reversed by the selective caspase inhibitor, Z-VAD-FMK. Furthermore, immunoblotting analysis indicated that ectopic expression of WWOX could trigger the intrinsic apoptotic signaling pathway characterized by a down-regulation of Bcl-2 and Bcl-xL, and up-regulation of Bax and Cytochrome c along with a remarkable activation of the caspase cascades. Taken together, our data reveal that WWOX behaves as a potent tumor suppressor in CNE2 cells, possibly by enhancing apoptosis and weakening metastasis via the intrinsic apoptotic pathway.