title: Flufenamic acid promotes angiogenesis through AMPK activation.
abstract: Angiogenesis plays critical roles in development, tumor growth and metastasis. Flufenamic acid (FFA) is an anti-inflammatory agent known to alter ion fluxes across the plasma membrane. Its role in angiogenesis has not been fully addressed to date. Here, we report that FFA treatment promotes angiogenesis both in vitro and in vivo. Applying FFA for 12 h promoted tube formation of human umbilical vein endothelial cells (HUVECs) without affecting cell proliferation. Three angiogenesis-related genes, VEGF, e-NOS and AAMP, were analyzed by RT-PCR. A significant difference was found between the FFA group and the control; the FFA group had significantly higher mRNA accumulation levels of all the three genes (p<0.05). Moreover, in the chick embryo chorioallantoic membrane (CAM) assay, FFA promoted the formation of macroscopic blood vessels. Finally, western blotting showed that the FFA-treated group had significantly higher phosphorylated AMPK levels, compared with the control (p<0.05). These results suggest that FFA promotes angiogenesis both in vitro and in vivo likely via promoting tube formation through AMPK activation.
authors.affiliation: Division of Hepatic Surgery Ⅱ, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Ruiliang
authors.initials: R
authors.lastname: Ge
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.forename: Yilin
authors.initials: Y
authors.lastname: Tai
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
authors.forename: Gongtian
authors.initials: G
authors.lastname: Wei
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005439:Flufenamic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C093492:AAMP protein, human; D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005439:Flufenamic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases