Abstract
Background: Breast cancer is one of the most common global malignancy with high rate of mortality and morbidity. Objectives: This study aimed to evaluation of the effect of melittin on autophagy induced by everolimus in breast cancer cells. Methods: MCF-7 cell line was treated with some concentrations of melittin and everolimus, and according to the IC50, the cells were treated to IC50 dose, higher and lower doses than IC50 in combination or separately. Then, combination index (CI), dose reduction index parameters, and occurrence of autophagy were evaluated. Also, the expression levels of genes related to the autophagy pathway were investigated. Results: The results of this study indicated that melittin and everolimus decreased viability in a concentration- and time-dependent manner, and the combined treatment had a synergistic effect. After 24 hr treatment with IC50 concentration, autophagy was decreased significantly in the combined group compared to the group treated with everolimus (P < 0.05). Also the results of molecular analysis confirmed the data. Conclusions: Melittin reduces the resistance of human breast cancer cells or increases their sensitivity to everolimus through blocking of autophagy process and consequently more breast cancer cells eliminate.
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