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Drug Res (Stuttg) 2018; 68(12): 710-716
DOI: 10.1055/a-0631-8046
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Mina Chatran
1   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Younes Pilehvar-Soltanahmadi
1   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3   Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Mehdi Dadashpour
1   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Leila Faramarzi
1   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Sara Rasouli
2   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Davoud Jafari-Gharabaghlou
4   Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
,
Navid Asbaghi
2   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Nosratollah Zarghami
1   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3   Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4   Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 31 August 2017

accepted 15 May 2018

Publication Date:
19 June 2018 (online)

Also available at
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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.

Key words

Breast cancer - Synergistic effect - Metformin - Silibinin - hTERT
 

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