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Iranian Journal of Medical Sciences، جلد ۴۴، شماره ۲، صفحات ۹۹-۱۰۷
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عنوان انگلیسی Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism
چکیده انگلیسی مقاله 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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نویسندگان مقاله Abbas Shafaee |
Department of Radiology-Faculty of Paramedicine- Tabriz University of Medical Sciences, Tabriz, Iran

Jalil Pirayesh Islamian |
Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Davoud Zarei |
Department of Medical Radiation Science, School of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Mohsen Mohammadi |
Department of Medical Radiation Science, School of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Kazem Nejati-Koshki |
Department of Medical Biotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

Alireza Farajollahi |
Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Seyed Mahmoud Reza Aghamiri |
Department of Radiation Medicine, Faculty of Nuclear Engineering, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Mohammad Rahmati Yamchi |
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Behzad Baradaran |
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Mohammad Asghari Jafarabadi |
Department of Statistics and Epidemiology, Tabriz University of Medical Sciences, Tabriz, Iran

نشانی اینترنتی http://ijms.sums.ac.ir/article_44522_dad6330c5cbad87e6bb567e718f52b72.pdf
فایل مقاله اشکال در دسترسی به فایل - ./files/site1/rds_journals/147/article-147-1611411.pdf
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