In this research, we evaluated the molecular mechanism of the effect of metformin in the radio sensitivity of breast cancer cells. This research was done in cellular and molecular research center of Qazvin University of Medical Science from 2020 to 2022. The studied samples were two breast cancer cell lines (MCF-7 and MDA-MB-231) they are derived from primary and secondary tumors resected from a single patient. We exposed them to cumulative 50 Gy radiation and constructed radio-resistant cell lines. Then resistant cell lines were treated with 50µm of metformin. Our studied groups were resistant cells treated and untreated with metformin. Then, the expression rate of miR-21-5p and SESN1 gene in resistant and control cells was checked by Quantitative Real-time PCR (qRTPCR). After the cell lines were treated with different concentrations of metformin at different intervals, the rate of cell proliferation and cell death was checked by CCK-8 assay and flow cytometry. The Western blot method was also used to confirm the expression of some genes. Our results showed that the expression of miR-21-5p was upregulated in radiation-resistant cancer cells (1.8±0.65) (P<0.0001) MCF-7 cell line and (1.6±0.42)(P<0.0001) MBA-MD-231 cell line, while the expression of SESN1 was down-regulated (0.46±0.12) (P<0.0001) MCF-7 cell line and (0.42±0.22) (P<0.001) MBA-MD-231 cell line. Metformin enhanced the radio sensitivity of breast cancer cells in a dose and time-dependent manner. Also, metformin treatment decreased the expression of miR-21-5p (0.47±0.32) (P<0.0001) MCF-7 cell line and (0.45±0.21) (P<0.0001) MBA-MD-231 cell line and increased the expression of SESN1 (1.65±0.72) (P<0.0001) MCF-7 cell line and (1.73±0.52) (P<0.0001) MBA-MD-231 cell line. The function of metformin was reversed by miR-21-5p inhibitors or the transfection of SESN1 overexpressing plasmids.

Conclusion: In conclusion, based on this research results, metformin enhanced the radio sensitivity of breast cancer cells via modulating the expression of miR-21-5p and SESN1. 

Sahar Moghbelinejad completed her PhD in 2011 from Tarbiat Modares University, Iran. She is an associate professor of medical genetics at Qazvin University of Medical Sciences. She has over 50 publications that have been cited over 800 times, and her publication H-index is 11. She is editor-in-chief of the Journal of Inflammatory Diseases (The Journal of Qazvin University of Medical Science).