Marjan Hajimoradi Javarsiani - Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
Shagayegh Haghjooy Javanmard - Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
Javad Sajedianfard - Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

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 B۱۶f۱۰ was treated with dacarbazine IC۵۰, metformin in different doses (۰.۵, ۲ and ۸ 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 B۱۶-F۱۰ cells; cell viability, determined at various time intervals (۲۴ and ۴۸ h) and in the presence of different drug concentrations (≅۰.۷μM), was reduced by ~۵۰% following ۲۴ h. The proliferation rate was evaluated over ۲۴-۴۸ hours and ۱۲ days using varying subcytotoxic and cytotoxic concentrations of metformin (۲-۸μM), 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 B۱۶-F۱۰ cells showed that the drug combination induces significantly more apoptosis compared with when each drug is individually used. B۱۶F۱۰ 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.

Melanoma, Combination Therapy, Metformin, Colonization