Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism

Background: both mitochondrial dysfunction and aerobic glycolysis are signs of growing aggressive cancer. if altered metabolism of cancer cell is intended, using the glycolysis inhibitor (2-deoxyglucose (2dg)) would be a viable therapeutic method. the amp-activated protein kinase (ampk), as a metabolic sensor, could be activated with metformin and it can also launch a p53-dependent metabolic checkpoint and might inhibit cancer cell growth. methods: after treatment with 5 mm metformin and/or 500 μm 2dg, the te1, te8, and te11 cellular viability and apoptosis were assessed by mtt, tunel, and elisa methods. the changes in p53 and bcl-2 genes expression levels were examined using real-time pcr method. data were analyzed by kruskal-wallis test using the spss 17.0 software. results: metformin and 2dg, alone and in combination, induced apoptosis in the cell lines. real-time pcr revealed that metformin induced apoptosis in te8 and te11 cells by activating p53, down-regulating bcl-2 expression. the induced apoptosis by 2dg raised by metformin and the combination modulated the expression of bcl-2 protein in all cell lines and it was more effective in te11 cell line. conclusion: metformin induced apoptosis in escc by down-regulating bcl-2 expression, and up-regulating p53 and induced apoptosis increased by 2-deoxy-d-glucose. thus, the combination therapy is an effective therapeutic strategy for esophageal squamous cell carcinoma.