Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression

The use of glucagon-like peptide-1 analogues, such as liraglutide, as hypoglycemic drugs has been widely employed in clinical practice. Liraglutide is reported to exert potential anti-breast cancer effects, however the specific mechanisms of this action remain unknown. In the present study, MCF-7 human breast cancer cells were cultured in vitro and treated with various concentrations of liraglutide. Cell Counting Kit-8, colony formation and flow cytometry assays were performed to determine the proliferation and apoptosis of cells following treatment. Furthermore, reverse transcription-quantitative polymerase chain reaction was employed to measure the expression level of microRNA (miRNA/miR)-27a. In addition, miR-27a mimics, inhibitors and negative controls were transfected into MCF-7 cells and the proliferation and apoptosis of cells following transfection was subsequently determined. Western blotting was performed to detect alterations in the protein expression of AMP-activated protein kinase catalytic subunit α2 (AMPKα2), proliferating cell nuclear antigen and cleaved-caspase-3 following treatments. The results demonstrated that, following treatment with liraglutide, the proliferation of MCF-7 cells was reduced and the apoptosis was increased, compared with the control group; this effect was increased with increasing concentrations of liraglutide. In addition, liraglutide treatment downregulated miR-27a expression in MCF-7 cells. While the overexpression of miR-27a promoted cell proliferation and inhibited apoptosis, knockdown of endogenous miR-27a inhibited cell proliferation and promoted apoptosis in MCF-7 cells. Furthermore, the expression of AMPKα2 protein in the group transfected with miR-27a mimics was decreased, while it was increased in MCF-7 cells transfected with miR-27a inhibitors. In conclusion, liraglutide may have a role in the inhibition of proliferation and promotion of apoptosis in MCF-7 cells. Concerning the mechanism of these effects, liraglutide may inhibit miR-27a expression, which subsequently increases the expression of AMPKα2 protein. The present study provides an experimental basis for the clinical treatment strategies of T2DM patients with breast cancer.