Jafari-Gharabaghlou Davoud, Pilehvar-Soltanahmadi Younes, Dadashpour Mehdi, Mota Ali, Vafajouy-Jamshidi Soheila, Faramarzi Leila, Rasouli Sara, Zarghami Nosratollah
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Basic Med Sci. 2018 Nov;21(11):1167-1173. doi: 10.22038/IJBMS.2018.30460.7345.
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.
Cytotoxicity of the drugs individually and in combination against T47D and MDA-MB-231 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 48 hr drug exposure were determined using qRT-PCR.
Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDA-MB-231 cells compared with T47D cells. It was found that MET+PHE reduced the IC50s 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 IC50 values against MDA-MB-231 cells than against T47D 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-231cells than in T47D cells (<0.001).
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.
乳腺癌仍然是一项全球性挑战，当下仍迫切需要进一步的化学预防疗法。新出现的证据显示了双胍类药物二甲双胍（MET）和苯乙双胍（PHE）具有强大的抗癌作用。因此，为探索一种有效的乳腺癌化学预防策略，评估了MET与PHE联合使用对乳腺癌细胞的抗增殖作用。
采用MTT法评估药物单独及联合使用对T47D和MDA-MB-231乳腺癌细胞的细胞毒性，并使用中位效应法分析MET与PHE之间相互作用的确切性质。此外，通过qRT-PCR测定药物暴露48小时后hTERT的表达水平。
基于细胞毒性试验，与T47D细胞相比，MET和PHE均进一步抑制了MDA-MB-231细胞的生长。结果发现，MET+PHE以协同方式大幅降低了两种细胞中MET和PHE的半数抑制浓度（IC50），比单一治疗效果更显著。重要的是，MET+PHE对MDA-MB-231细胞显示出更高的抗增殖作用，IC50值更小，优于对T47D细胞的作用。实时PCR结果显示，与单一治疗相比，MET+PHE处理的两种乳腺癌细胞系中hTERT表达均显著降低。在两种乳腺癌细胞之间进行比较时，发现MET+PHE在MDA-MB-231细胞中比在T47D细胞中能进一步降低hTERT表达（<0.001）。
推测MET与PHE联合使用可能是一种有前景且便捷的方法，可提高乳腺癌治疗效率。推测MET与PHE联合使用可能是一种有前景且便捷的方法，可提高乳腺癌治疗效率。
