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

Abstract

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.

Identification of chemoresistance-associated miRNAs in breast cancer

“…It has been widely acknowledged that miRNAs, a class of small endogenous noncoding RNAs, are frequently dysregulated in breast cancer. The abnormal expression of miRNAs is closely associated with the occurrence and development of breast cancer, such as proliferation, 18 apoptosis, 19 angiogenesis, 20 and metastasis. 21 Recently, our group has found that miR-20a and miR-27b were involved in chemoresistance of breast cancer.…”

MicroRNA-27a (miR-27a) in Solid Tumors: A Review Based on Mechanisms and Clinical Observations

“…Arsenic trioxide, a widely used anticancer drug in leukemia, was found to suppress cell growth and migration via the inhibition of miR-27a in breast cancer cells, providing a novel antitumor mechanism in miR-27a for the treatment of breast cancer (121). In addition, one novel study showed that liraglutide inhibited the proliferation and promoted the apoptosis of MCF-7 breast cancer cell lines through the downregulation of microRNA-27a expression (122). These studies provide a new method of drug design and a novel use of traditional drugs.…”

Growth Promotion and Increased ATP-Binding Cassette Transporters Expression by Liraglutide in Triple Negative Breast Cancer Cell Line MDA-MB-231

“…Several evidences obtained from in vitro studies indicate that GLP-1 agonists can exert growth inhibition effects on breast cancer lines [12,13,16]. However, these investigations were mostly done by either exenatide (exendine-4), the first widely used GLP-1 agonist, or on the MCF-7 cell line, which represents a poorly aggressive and non-invasive phenotype [17] of breast cancer.…”