Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy |
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Authors: | Ommoleila Molavi Farzaneh Narimani Farshid Asiaee Simin Sharifi Vahideh Tarhriz Ali Shayanfar |
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Affiliation: | 1. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran;3. Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada;4. Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran |
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Abstract: | Context: Multiple drug resistance is the major obstacle to conventional chemotherapy. Silibinin, a nontoxic naturally occurring compound, has anticancer activity and can increase the cytotoxic effects of chemotherapy in various cancer models.Objective: To evaluate the effects of silibinin on enhancing the sensitivity of chemo-resistant human breast cell lines to doxorubicin (DOX) and paclitaxel (PAC).Materials and methods: The cells were treated with silibinin (at 50 to 600?μM concentrations) and/or chemo drugs for 24 and 48?h, then cell viability and changes in oncogenic proteins were determined by MTT assay and Western blotting/RT-PCR, respectively. Flow cytometry was used to study apoptosis in the cells receiving different treatments. The antitumorigenic effects of silibinin (at 200 to 400?μM concentration) were evaluated by mammosphere assay.Results: Silibinin exerted significant growth inhibitory effects with IC50 ranging from 200 to 570?μM in different cell lines. Treatment of DOX-resistant MDA-MB-435 cells with silibinin at 200?μM reduced DOX IC50 from 71 to 10?μg/mL and significantly suppressed the key oncogenic pathways including STAT3, AKT, and ERK in these cells. Interestingly treatment of DOX-resistant MDA-MB-435 cells with silibinin at 400?μM concentration for 48?h induced a 50% decrease in the numbers of colonies as compared with DMSO-treated cells. Treatment of PAC-resistant MCF-7 cells with silibinin at 400?μM concentration generated synergistic effects when it was used in combination with PAC at 250?nM concentration (CI?=?0.81).Conclusion: Silibinin sensitizes chemo-resistant cells to chemotherapeutic agents and can be useful in treating breast cancers. |
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Keywords: | Resistance doxorubicin paclitaxel apoptosis STAT3 pathway |
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