Effect of metformin on the proliferation, migration, and MMP-2 and -9 expression of human umbilical vein endothelial cells

Esfahanian,Nilufar; Shakiba,Yadollah; Nikbin,Behroz; Soraya,Hamid; Maleki-Dizaji,Nasrin; Ghazi-Khansari,Mahmood; Garjani,Alireza

doi:10.3892/mmr.2012.753

Effect of metformin on the proliferation, migration, and MMP-2 and -9 expression of human umbilical vein endothelial cells

Authors:
- Nilufar Esfahanian
- Yadollah Shakiba
- Behroz Nikbin
- Hamid Soraya
- Nasrin Maleki-Dizaji
- Mahmood Ghazi-Khansari
- Alireza Garjani
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Affiliations: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Published online on: January 12, 2012 https://doi.org/10.3892/mmr.2012.753
Pages: 1068-1074

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Abstract

Recent epidemiological studies have demonstrated that metformin lowers the risk of several types of cancer in diabetic patients. Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the vascular basement membrane extracellular matrix proteins, thereby promoting endothelial cell invasion, migration and angiogenesis in the incidence and progression of tumors. The aim of this study was to investigate the effects of metformin on human umbilical vein endothelial cell (HUVEC) proliferation and migration, as well as on MMP-2 and MMP-9 expression. Cell proliferation was determined by cell counting and MTT colorimetric assays. Cell migration was assessed by the wound repair method. Quantitative real-time reverse transcription PCR was performed to quantify the mRNA expression of MMPs. Metformin at concentrations of 0.5-3.0 mM effectively reduced the number of endothelial cells by 5.5-55%, without being cytotoxic to the cells. Similarly, cell proliferation and migration were markedly inhibited by metformin. In addition, treatment with metformin demonstrated a strong (P<0.001) suppressive effect on the mRNA levels of MMP-2 and -9 in the endothelial cells. The inhibitory effects of metformin on endothelial cell number, migration, and MMP expression were reversed partially by compound C, which is an inhibitor of AMP-activated protein kinase (AMPK). The present study reports that metformin considerably inhibited the proliferation, migration, and MMP-2 and -9 expression of HUVECs, and the effect was partially AMPK-dependent. The obtained findings provide a molecular rationale, whereby metformin can exert anticancer effects.

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