Document Type : Original Article(s)
Authors
- Abbas Shafaee 1
- Jalil Pirayesh Islamian 2
- Davoud Zarei 3
- Mohsen Mohammadi 3
- Kazem Nejati-Koshki 4
- Alireza Farajollahi 2
- Seyed Mahmoud Reza Aghamiri 5
- Mohammad Rahmati Yamchi 6
- Behzad Baradaran 7
- Mohammad Asghari Jafarabadi 8
1 Department of Radiology-Faculty of Paramedicine- Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Medical Radiation Science, School of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Medical Biotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
5 Department of Radiation Medicine, Faculty of Nuclear Engineering, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
7 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
8 Department of Statistics and Epidemiology, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
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.
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