Mina Chatran 1 , Younes Pilehvar-Soltanahmadi 1,2,3 , Mehdi Dadashpour 1,2 , Leila Faramarzi 1,2 , Sara Rasouli 2 , Davoud Jafari-Gharabaghlou 4 , Navid Asbaghi 2 , Nosratollah Zarghami 1,2,3,4 Show Affiliations »
Abstract
BACKGROUND: 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. OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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. © Georg Thieme Verlag KG Stuttgart · New York.
BACKGROUND: 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. OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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. © Georg Thieme Verlag KG Stuttgart · New York.
Entities: Chemical
Disease
Gene
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Year: 2018
PMID： 29920623 DOI： 10.1055/a-0631-8046
Source DB: PubMed Journal: Drug Res (Stuttg) ISSN： 2194-9379