Anti-angiogenic Effects of Metformin, an AMPK Activator, on Human Umbilical Vein Endothelial Cells and on Granulation Tissue in Rat | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 13، دوره 15، شماره 6، بهمن 2012، صفحه 1202-1209 اصل مقاله (298.38 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2012.4941 | ||
| نویسندگان | ||
| Hamid Soraya1؛ Nilufar Esfahanian1؛ Yadollah Shakiba2؛ Mahmood Ghazi-Khansari3؛ Behroz Nikbin2؛ Hasan Hafezzadeh1؛ Nasrin Maleki Dizaji1؛ Alireza Garjani* 1 | ||
| 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 2Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran | ||
| 3Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran | ||
| چکیده | ||
| 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 Methods A "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. Results Metformin (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. Conclusion The present study reported that metformin inhibited endothelial cell migration and angiogenesis in vitro and in vivo, and the effect was partially AMPK dependent. | ||
| کلیدواژهها | ||
| Angiogenesis؛ Endothelial cells, Metformin, Migration, Proliferation | ||
| مراجع | ||
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