Chatran Mina, Pilehvar-Soltanahmadi Younes, Dadashpour Mehdi, Faramarzi Leila, Rasouli Sara, Jafari-Gharabaghlou Davoud, Asbaghi Navid, Zarghami Nosratollah
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Res (Stuttg). 2018 Dec;68(12):710-716. doi: 10.1055/a-0631-8046. Epub 2018 Jun 19.
There is a growing body of data that chemotherapeutic combination strategies would be more effective in reducing drug toxicity, inhibiting tumor progression in comparison to either drug alone.
To explore a chemopreventive strategy for improving breast cancer treatment efficacy, the anticancer effects of a combination of Metformin (MET) and Silibinin (SIL) were investigated in T47D breast cancer cells.
Cytotoxicity of the drugs individually and in combination was evaluated using MTT assay. The precise nature of the interaction between MET and SIL was further analyzed through the median-effect method. In addition, qRT-PCR was applied to determine the expression levels of hTERT and cyclin D1 genes after 48 h drug exposure.
MTT assays showed that MET and SIL individually inhibited the cell viability in a dose and time-dependent manner, and the obtained combination indices (CIs) were<1 for all the combination treatments, indicating that the anticancer agents synergistically induced growth inhibition in the breast cancer cells. qPCR findings revealed that the drug combination also synergistically down-regulated the expression levels of hTERT and cyclin D1 at all used concentrations compared with the drugs used alone after 48 h treatment (P≤0.05).
The results provide evidence that synergistic antiproliferative effects of MET and SIL, linking to the down-regulation of Cyclin D1 and hTERT genes, and propose that MET+SIL may have therapeutic value in breast cancer therapy.
越来越多的数据表明，与单独使用任何一种药物相比，化疗联合策略在降低药物毒性、抑制肿瘤进展方面可能更有效。
为探索一种提高乳腺癌治疗疗效的化学预防策略，研究了二甲双胍（MET）和水飞蓟宾（SIL）联合应用于T47D乳腺癌细胞的抗癌作用。
采用MTT法评估药物单独及联合应用时的细胞毒性。通过中位效应法进一步分析MET与SIL之间相互作用的具体性质。此外，应用qRT-PCR检测药物作用48小时后hTERT和细胞周期蛋白D1基因的表达水平。
MTT试验表明，MET和SIL单独应用时均以剂量和时间依赖性方式抑制细胞活力，所有联合治疗的联合指数（CI）均<1，表明抗癌药物在乳腺癌细胞中协同诱导生长抑制。qPCR结果显示，与单独用药相比，48小时治疗后，所有使用浓度的药物联合应用也协同下调了hTERT和细胞周期蛋白D1的表达水平（P≤0.05）。
结果表明MET和SIL具有协同抗增殖作用，与细胞周期蛋白D1和hTERT基因的下调有关，并提示MET+SIL在乳腺癌治疗中可能具有治疗价值。
