Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells

Davoud Jafari-Gharabaghlou; Younes Pilehvar-Soltanahmadi; Mehdi Dadashpour; Ali Mota; Soheila Vafajouy-Jamshidi; Leila Faramarzi; Sara Rasouli; Nosratollah Zarghami

Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells

محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 21، شماره: 11

سال انتشار: 1397

نوع سند: مقاله ژورنالی

زبان: انگلیسی

مشاهده: 237

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علوم پزشکی > سرطان

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لینک ثابت به این مقاله:

https://civilica.com/doc/1295204

شناسه ملی سند علمی:

JR_IJBMS-21-11_011

تاریخ نمایه سازی: 27 مهر 1400

چکیده مقاله:

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.

کلیدواژه ها:

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

نویسندگان

Davoud Jafari-Gharabaghlou