Metformin-induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16

Hao,Biao; Xiao,Yan; Song,Fang; Long,Xiangshu; Huang,Jing; Tian,Maobo; Deng,Shiyan; Wu,Qiang

doi:10.3892/ijmm.2017.3346

Metformin-induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16

Authors:
- Biao Hao
- Yan Xiao
- Fang Song
- Xiangshu Long
- Jing Huang
- Maobo Tian
- Shiyan Deng
- Qiang Wu
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Affiliations: Department of Cardiology, The Affiliated People's Hospital of Guizhou Medical University, Guiyang, Guizhou 550002, P.R. China
Published online on: December 22, 2017 https://doi.org/10.3892/ijmm.2017.3346
Pages: 1365-1376
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The proliferation and migration of vascular smooth muscle cells are significant in the development and progression of atherosclerosis and plaque rupture. Metformin is a widely used antidiabetic drug, which has been reported to inhibit cell growth and migration. The antiproliferative and antimigratory effects of metformin have been attributed to 5' adenosine monophosphate-activated protein kinase (AMPK) activation. The purpose of the present study was to investigate the effects of metformin on primary human aortic muscle cells (HASMCs) in vitro and to clarify the underlying mechanism. We investigated the effectiveness of metformin in inhibiting the proliferation and migration of HASMCs in vitro using RNA extraction and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell number counting, cell viability assay, cell cycle assay and cell migration assay. Through transfection with small interfering (si)RNA targeting p53 and interferon‑inducible protein 16 (IFI16), the roles of p53 and IFI16 in these processes were evaluated. The present study demonstrated that p53, IFI16 and AMPK were upregulated in senescent primary HASMCs, which exhibited a decrease in proliferation and migration. In addition, metformin was able to activate p53, IFI16 and AMPK, in order to inhibit proliferation and migration of HASMCs. Furthermore, siRNA‑mediated knockdown of p53 and IFI16 attenuated AMPK activation and reversed the suppressive effects of metformin. Notably, in response to metformin, the activation of AMPK was not observed in p53‑ and IFI16‑silenced HASMCs. These results indicated that metformin-induced activation of AMPK suppresses the proliferation and migration of HASMCs by upregulating p53 and IFI16. These findings suggested that metformin may have potential use in the treatment of atherosclerosis.

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