Synergistic Anti-proliferative Effects of Metformin and Silibinin Combination on T47D Breast Cancer Cells via hTERT and Cyclin D1 Inhibition.

Abstract

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.