2-Deoxyglucose as a therapeutic strategy for EBV-associated gastric carcinoma: Glycolytic and lytic reactivation inhibition under hypoxic conditions

Epstein-Barr virus-associated gastric carcinoma (EBVaGC), a distinct subtype of gastric cancer, accounts for approximately 10 % of all gastric cancer cases. 2-deoxyglucose (2-DG), a glycolysis inhibitor, has emerged as a crucial tool in cancer therapy. However, the differential effects of 2-DG on EBVaGC and EBV-negative gastric carcinoma (EBVnGC) are not yet fully understood. In this study, we demonstrated that 2-DG inhibited the proliferation of both AGS and AGS-EBV cells, with AGS-EBV cells exhibiting greater sensitivity, particularly under hypoxic conditions. Furthermore, EBV infection was found to upregulate glycolytic gene expression in AGS-EBV cells, particularly under hypoxic conditions, through HIF-1α-dependent mechanisms. Notably, 2-DG also inhibited EBV lytic reactivation in AGS-EBV cells under hypoxic conditions. These findings provide valuable insights into the molecular mechanisms of EBV-mediated metabolic reprogramming and highlight the potential of 2-DG as a therapeutic agent for EBVaGC.