TY - JOUR ID - 4941 TI - Anti-angiogenic Effects of Metformin, an AMPK Activator, on Human Umbilical Vein Endothelial Cells and on Granulation Tissue in Rat JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Soraya, Hamid AU - Esfahanian, Nilufar AU - Shakiba, Yadollah AU - Ghazi-Khansari, Mahmood AU - Nikbin, Behroz AU - Hafezzadeh, Hasan AU - Maleki Dizaji, Nasrin AU - Garjani, Alireza AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran AD - Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Y1 - 2012 PY - 2012 VL - 15 IS - 6 SP - 1202 EP - 1209 KW - Angiogenesis KW - Endothelial cells, Metformin, Migration, Proliferation DO - 10.22038/ijbms.2012.4941 N2 - Objective(s)Metformin is well known for activation of AMP-activated protein kinase (AMPK). AMPK activation inhibits mammalian target of rapamycin (mTOR) as a key signaling process in cell proliferation. Recent epidemiological studies demonstrate that metformin lowers the risk for several types of cancer in diabetic patients. Concerning the critical role of angiogenesis in the incidence and progression of tumors, we investigated the effect of metformin on human umbilical vein endothelial cells migration, as well as on vascular endothelial growth factor (VEGF) expressions in the cells and also on angiogenesis in air pouch model in rats.Materials and MethodsA "wound" repair method was used to assess the cell migration (n=6). Real-time PCR was performed to quantify the mRNA expression of VEGF (n=5). In air pouch model, carrageenan was injected into the air pouches on the back of rats (n=6) and following an IV injection of carmine red dye granulomatous tissue was processed for the assessment of the dye content. An ordinary ANOVA with Student-Newman-Keuls post hoc test was used to compare groups.ResultsMetformin (orally, 50mg/kg) significantly (P<0.01) decreased angiogenesis in granulomatous tissue by 34% in pouch-bearing rats. Metformin at concentrations of 0.5-3 mM significantly (P<0.001) inhibited VEGF mRNA expression and endothelial cell migration. The inhibitory effects of metformin on the endothelial cell migration were reversed partially by compound C (P<0.01), an inhibitor of AMPK.ConclusionThe present study reported that metformin inhibited endothelial cell migration and angiogenesis in vitro and in vivo, and the effect was partially AMPK dependent. UR - https://ijbms.mums.ac.ir/article_4941.html L1 - https://ijbms.mums.ac.ir/article_4941_eb9ee9ccdfdf7416c10296d2fd91646a.pdf ER -