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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 hu...

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Autores principales: Zhao, Wei, Zhang, Xiaohui, Zhou, Zhichao, Sun, Bei, Gu, Wenyuan, Liu, Jia, Zhang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865986/
https://www.ncbi.nlm.nih.gov/pubmed/29393459
http://dx.doi.org/10.3892/mmr.2018.8475
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author Zhao, Wei
Zhang, Xiaohui
Zhou, Zhichao
Sun, Bei
Gu, Wenyuan
Liu, Jia
Zhang, Hong
author_facet Zhao, Wei
Zhang, Xiaohui
Zhou, Zhichao
Sun, Bei
Gu, Wenyuan
Liu, Jia
Zhang, Hong
author_sort Zhao, Wei
collection PubMed
description 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.
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spelling pubmed-58659862018-03-28 Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression Zhao, Wei Zhang, Xiaohui Zhou, Zhichao Sun, Bei Gu, Wenyuan Liu, Jia Zhang, Hong Mol Med Rep Articles 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. D.A. Spandidos 2018-04 2018-01-24 /pmc/articles/PMC5865986/ /pubmed/29393459 http://dx.doi.org/10.3892/mmr.2018.8475 Text en Copyright: © Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhao, Wei
Zhang, Xiaohui
Zhou, Zhichao
Sun, Bei
Gu, Wenyuan
Liu, Jia
Zhang, Hong
Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression
title Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression
title_full Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression
title_fullStr Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression
title_full_unstemmed Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression
title_short Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression
title_sort liraglutide inhibits the proliferation and promotes the apoptosis of mcf-7 human breast cancer cells through downregulation of microrna-27a expression
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865986/
https://www.ncbi.nlm.nih.gov/pubmed/29393459
http://dx.doi.org/10.3892/mmr.2018.8475
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