Document Type : Original Article
Department of Cellular and Molecular Biology and Microbology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
Department of Biology, Shahid Bahonar University of Kerman, Kerman, Iran
Insulin induces anti-cancer drugs resistance in tumor cells. However, the mechanism by which insulin induces its drug resistance effects is not clear. In the present study, the expression of miR-221 in insulin-treated MCF-7 cells in response to the anti-cancer drug doxorubicin, was investigated.
Materials and Methods
In this experimental study, cell viability was evaluated using MTT (3-[4,5 dimethylthiazol-2- yl]-2,5-diphenyl tetrazolium bromide) assay. The expression level of miR-221 was determined by real time polymerase chain reaction (RT-PCR). Furthermore, the expression of insulin receptor (IR) and cleaved caspase-3 protein was assessed by Western blotting.
The results showed that treatment of the MCF-7 cells with insulin reduced the anti-cancer effects of doxorubicin. Viability of naive and insulin-treated cells following doxorubicin (DOX) treatment was 62.9 ± 5.7% and 79 ± 7.2%, respectively. Furthermore, the expression of miR-221 in insulin-treated cells was significantly increased (2.6 ± 0.37-fold change) as compared with the control group. A significant decrease (26%) in the expression of caspase-3 protein and a significant increase (24%) in IR were observed in insulin-induced drug resistant MCF-7 cells as compared to the naive cells.
Together, the data showed a positive correlation between the expression of miR-221 and IR expression, but a negative correlation with caspase3 expression, in insulin-induced drug resistant MCF-7 breast cancer cells. This could suggest a new mechanism for the role of miR-221 in cancer drugs resistance induced by insulin.