PMID- 23653852
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130509
LR  - 20211021
IS  - 2008-3866 (Print)
IS  - 2008-3874 (Electronic)
IS  - 2008-3866 (Linking)
VI  - 15
IP  - 6
DP  - 2012 Nov
TI  - Anti-angiogenic Effects of Metformin, an AMPK Activator, on Human Umbilical Vein 
      Endothelial Cells and on Granulation Tissue in Rat.
PG  - 1202-9
AB  - OBJECTIVES: 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.
FAU - Soraya, Hamid
AU  - Soraya H
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University 
      of Medical Sciences, Tabriz, Iran.
FAU - Esfahanian, Nilufar
AU  - Esfahanian N
FAU - Shakiba, Yadollah
AU  - Shakiba Y
FAU - Ghazi-Khansari, Mahmood
AU  - Ghazi-Khansari M
FAU - Nikbin, Behroz
AU  - Nikbin B
FAU - Hafezzadeh, Hasan
AU  - Hafezzadeh H
FAU - Maleki Dizaji, Nasrin
AU  - Maleki Dizaji N
FAU - Garjani, Alireza
AU  - Garjani A
LA  - eng
PT  - Journal Article
PL  - Iran
TA  - Iran J Basic Med Sci
JT  - Iranian journal of basic medical sciences
JID - 101517966
PMC - PMC3646233
OTO - NOTNLM
OT  - Angiogenesis; Endothelial cells
OT  - Metformin
OT  - Migration
OT  - Proliferation
EDAT- 2013/05/09 06:00
MHDA- 2013/05/09 06:01
PMCR- 2012/11/01
CRDT- 2013/05/09 06:00
PHST- 2011/12/01 00:00 [received]
PHST- 2012/05/22 00:00 [accepted]
PHST- 2013/05/09 06:00 [entrez]
PHST- 2013/05/09 06:00 [pubmed]
PHST- 2013/05/09 06:01 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - IJBMS-15-1202 [pii]
PST - ppublish
SO  - Iran J Basic Med Sci. 2012 Nov;15(6):1202-9.