%0 Journal Article %T Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism %J Iranian Journal of Medical Sciences %I Shiraz University of Medical Sciences %Z 0253-0716 %A Shafaee, Abbas %A Pirayesh Islamian, Jalil %A Zarei, Davoud %A Mohammadi, Mohsen %A Nejati-Koshki, Kazem %A Farajollahi, Alireza %A Aghamiri, Seyed Mahmoud Reza %A Rahmati Yamchi, Mohammad %A Baradaran, Behzad %A Asghari Jafarabadi, Mohammad %D 2019 %\ 03/01/2019 %V 44 %N 2 %P 99-107 %! Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism %K 2-Deoxy-D-Glucose %K Esophageal carcinoma %K Metformin %K apoptosis %R 10.30476/ijms.2019.44522 %X 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. %U https://ijms.sums.ac.ir/article_44522_7ab70849b19909ee8dd86b721e96daba.pdf