Down-regulation of Notch signaling by a γ-secretase inhibitor enhances the radiosensitivity of nasopharyngeal carcinoma cells.

Currently, the main approach to nasopharyngeal carcinoma (NPC) treatment is radiotherapy (RT), but for many NPC patients, RT is not effective. Increasing RT sensitivity of NPC cells would provide a significant treatment advance for NPC patients. While γ-secretase inhibitors (GSIs) have gained recent attention as novel anticancer drugs, the mechanism of action of GSIs as radiosensitizers is not well understood. In the present study, radiation-induced anti-proliferative effects of the one GSI (N-[(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester, DAPT), on CNE2 cells were investigated with the MTT assay; in vitro radiosensitization effects were evaluated by the apoptosis assay and the cell colony formation assay. The activation status of the Notch signaling pathway in DAPT- or dimethyl sulfoxide-treated CNE2 cells was also examined. Notch signaling in NPC cells was found to be down-regulated by DAPT; therefore, DAPT could significantly inhibit CNE2 growth and improve NPC radiosensitization, thus, enhancing RT-induced anti-proliferative effects and apoptosis. Taken together, our data show that Notch signaling down-regulation by GSIs could enhance radiosensitivity of NPC cells, suggesting clinical applications for GSIs as radiosensitizers for NPC therapy.