Document Type : Original Article(s)
Authors
1 Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
2 Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: Dacarbazine is considered as a standard treatment for melanoma, but resistance to anticancer therapy is a major cause of cancer stem cells invasion. In vitro assays have shown that metformin interferes with cell viability, proliferation, and apoptosis.
Method: Melanoma cell line B16f10 was treated with dacarbazine IC50, metformin in different doses (0.5, 2 and 8 mM) and combination therapy. The influence of treating and cell viability was determined with MTT assay, and the effect of treat on colonization was quantified. Changes in cleaved PARP were investigated using immunoblotting. The cytotoxicity effect of Dacarbazine was further analyzed.
Result: Metformin induced cytotoxicity on B16-F10 cells; cell viability, determined at various time intervals (24 and 48 h) and in the presence of different drug concentrations (≅0.7μM), was reduced by ~50% following 24 h. The proliferation rate was evaluated over 24-48 hours and 12 days using varying subcytotoxic and cytotoxic concentrations of metformin (2-8μM), which was reduced in a dose-dependent manner. Resistance cells resulted in slender spindles and better colonization. Finally, metformin decreased the cytotoxicity of dacarbazine and increased apoptosis.
Conclusion: A study with B16-F10 cells showed that the drug combination induces significantly more apoptosis compared with when each drug is individually used. B16F10 was the most sensitive and resistant at a normal dose of metformin and dacarbazine, which is a very encouraging result with regards to the possibility of metformin becoming a new tool for melanoma research and treatment.
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