چکیده انگلیسی مقاله |
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. |
نویسندگان مقاله |
حمید ثریا | hamid soraya department of pharmacology and toxicology, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)
نیلوفر اصفهانیان | nilufar esfahanian department of pharmacology and toxicology, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)
یداله شکیبا | yadollah shakiba department of immunology, school of medicine, tehran university of medical sciences, tehran, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)
محمود قاضی خوانساری | mahmood ghazi khansari department of pharmacology, school of medicine, tehran university of medical sciences, tehran, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)
بهروز نیک بین | behroz nikbin department of immunology, school of medicine, tehran university of medical sciences, tehran, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)
حسن حافظ زاده | hasan hafezzadeh department of pharmacology and toxicology, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)
نسرین مالکی دیزجی | nasrin maleki dizaji department of pharmacology and toxicology, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)
علیرضا گرجانی | alireza garjani department of pharmacology and toxicology, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran
سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)
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