Davoud Jafari-Gharabaghlou - Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Younes Pilehvar-Soltanahmadi - Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Mehdi Dadashpour - Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Ali Mota - Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Soheila Vafajouy-Jamshidi - Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Leila Faramarzi - Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Sara Rasouli - Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Nosratollah Zarghami - Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Objective(s): Breast cancer remains a global challenge, and further chemopreventive therapies are still immediately required. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET) and phenformin (PHE). Thus, to explore an efficient chemopreventive strategy for breast cancer, the antiproliferative effects of the combination of MET and PHE against breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the drugs individually and in combination against T۴۷D and MDA-MB-۲۳۱ breast cancer cells were assessed using MTT assay and the median-effect method was used to analyze the precise nature of the interaction between MET and PHE. Besides, the expression levels of hTERT after ۴۸ hr drug exposure were determined using qRT-PCR. Results: Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDA-MB-۲۳۱ cells compared with T۴۷D cells. It was found that MET+PHE reduced the IC۵۰s of MET and PHE in both cells drastically more than the single treatments in a synergistic manner. Importantly, MET+PHE showed higher antiproliferative effect with smaller IC۵۰ values against MDA-MB-۲۳۱ cells than against T۴۷D cells. Real-time PCR results revealed that hTERT expression was significantly reduced in both breast cancer cell lines treated with MET+PHE than the single treatments. In comparison between two types of breast cancer cells, it was detected that MET+PHE could further decline hTERT expression in MDA-MB-۲۳۱cells than in T۴۷D cells (P<۰.۰۰۱).Conclusion: It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment. It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.  

Breast Cancer, Combination therapy, Metformin, Phenformin, Synergistic effects