5-Aza-2′-deoxycytidine inhibits proliferation and induces apoptosis in oral cancer cells by enhancing glutathione peroxidase-3 expression

Background: Oral cancer is one of the most malignant cancers. Recent studies have suggested that glutathione peroxidase (GPX)-3 significantly affects the progression and prognosis of cancers. However, the function and mechanism of GPX3 in oral cancer are still unclear. Purpose: The aim of this study was to investigate the effects of 5-aza-2'-deoxycytidine (5-Aza-Cd) on the proliferation and apoptosis of oral cancer cells and the expression level of GPX-3. Materials and Methods: The methylation status and expression of GPX3 were analyzed using methylation-specific PCR (MSP) and qRT-PCR assays in normal oral epithelium cells (CAL-27) and oral cancer cells (HSC-3). CAL-27 and HSC-3 cells were treated with 20 mu mol/L 5-Aza-Cd, and GPX3 expression was measured by qRT-PCR assay. The methylation status of GPX3 was observed by methylation-specific PCR (MSP), and cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry. Results: Our results demonstrated that GPX3 expression was decreased, and methylation of the GPX3 promoter was increased in CAL-27 and HSC-3 cells compared with normal cells. The 5-Aza-Cd treatment upregulated GPX3 expression and downregulated methylation of the GPX3 promoter in CAL-27 and HSC-3 cells. In addition, 5-Aza-Cd inhibited proliferation and promoted apoptosis in oral cancer cells. Conclusions: Our results suggest that 5-Aza-Cd suppressed proliferation and accelerated apoptosis in oral cancer cells by inhibiting demethylation and thereby promoting GPX3 expression.