Evolution of the expression levels of mir-132 in MCF-7 breast cancer cells treated with Metformin loaded PLGA-PEG NPs, Possible relationship with hTERT expression

Introduction: Breast cancer is one of the most common cancers among women today. Currently, miRNAs are considered as attractive targets for therapeutic intervention in cancer prevention and therapy owing to their tumor suppressor or oncogenic action. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET). The aim of the present study was to evaluate the effect of pure MEt as well as the nano-formulation of this drug on the expression of mir-132 and telomerase in MCF-7 cell line.Material and methods: Nanoparticles are synthesized for controlled drug delivery and metformin is loaded onto the nanoparticles. Characterization of nanoformulated drugs was determined using DLS, FTIR, TEM, and SEM. Drug release study was performed using dialysis method. MTT and real-time PCR assays were applied to evaluate the cytotoxic effects of free and nano-encapsulated drugs on expression level of microRNA and hTERT in MCF-7 cells.Results: The results showed that free drugs and nano-formulations exhibited a dose-dependent cytotoxicity against MCF-7 cells cells and especially, MET–PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (P < 0.05). Real-time PCR results revealed that MET in free and encapsulated forms inhibited hTERT gene expression. Also, it was found that MET NPs than free forms could further increase Mir-132 expression and decrese hTERT expression in all concentration (P < 0.05).Conclusion: It is speculated that the nanofurmolation of MET may be a promising and convenient approach to improve the efficiency of breast cancer treatment. Moreover, these findings demonstrated that the nanodelivery of Met through targeting miR-132 might be a novel strategy for the treatment of breast cancer.

کلیدواژه ها:

mir-132 ، breast cancer cells ، Metformin ، PLGA-PEG NPs ، hTERT