Slug mediates nasopharyngeal carcinoma radioresistance via downregulation of PUMA in a p53-dependent and -independent manner.

Slug is involved in the radioresistance and chemoresistance of several types of cancers. In the present study, we first studied the effect of Slug on the radioresistance of nasopharyngeal carcinoma (NPC). We established radioresistant CNE-2 cells (CNE-2-RES) by exposing CNE-2 cells to gradually increasing doses of irradiation (IR). We used lentiviral infection technique to stably knock down Slug and then studied the effects in vitro and in vivo. Western blotting and RT-PCR were applied to detect the protein and mRNA expression in NPC cells or xenograft tumor tissues, respectively. Colony forming assay was applied to detect the cell survival after IR. As a result, CNE-2-RES cells were successfully established, CNE-2-RES cells showed relatively higher expression of Slug, higher expression of p53 and lower expression of PUMA. Following inhibition of Slug, the radiosensitivity of NPC was enhanced both in vitro and in vivo. Slug inversely regulated PUMA and p53 expression in both CNE-2 and CNE-2-RES cells. Animal experiments showed the same trend of protein expression as the in vitro results. In conclusion, our study demonstrated that Slug overexpression in CNE-2-RES cells may result in the radioresistance of cells. Slug mediates CNE-2 radioresistance via downregulation of PUMA in both a p53-dependent and p53-independent manner.