Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells 英文参考文献.docVIP

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Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells 英文参考文献.doc

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Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells 英文参考文献

PaeonolOximeInhibitsbFGF-InducedAngiogenesisand ReducesVEGFLevelsinFibrosarcomaCells Hyo-JeongLee1.,Seung-AeKim1.,Hyo-JungLee1.,Soo-JinJeong1.,IhnHan1,JiHoonJung1 ,Eun-Ok Lee1,ShudongZhu2,Chang-YanChen2,Sung-HoonKim1* 1CollegeofOrientalMedicine,KyungHeeUniversity,Seoul,RepublicofKorea,2BethIsraelDeaconessMedicalCenter,HarvardMedicalSchool,Boston,Massachusetts, UnitedStatesofAmerica Abstract Background:Wepreviouslyreportedtheanti-angiogenicactivityofpaeonolisolatedfromMoutanCortex.Inthepresent study,weinvestigatedthenegativeeffectofpaeonoloxime(PO,apaeonolderivative)onbasicfibroblastgrowthfactor (bFGF)-mediatedangiogenesisinhumanumbilicalveinendothelialcells(HUVECs)(includingtumorangiogenesis)andpro- survivalactivityinHT-1080fibrosarcomacellline. Methodology/Principal Findings: We showed that PO (IC50 =17.3mg/ml) significantly inhibited bFGF-induced cell proliferation,whichwasachievedwithhigherconcentrationsofpaeonol(IC50over200mg).ThetreatmentwithPOblocked bFGF-stimulatedmigrationandinvitrocapillarydifferentiation(tubeformation)inadose-dependentmanner.Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25mg/ml) decreased the cell viability of HT-1080 fibrosarcomacellsbutnotthatofHUVECs.ThetreatmentwithPOat12.5mg/mlreducedthelevelsofphosphorylatedAKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealedthatPOtreatmentattenuatedAKTphosphorylationinHT-1080cells. Conclusions/Significance: Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs anddecreasedthelevelsofPI3K,phospho-AKTandVEGFinHT-1080cells. Citation:LeeH-J,KimS-A,LeeH-J,JeongS-J,HanI,etal.(2010)PaeonolOximeInhibitsbFGF-InducedAngiogenesisandReducesVEGFLevelsinFibrosarcoma Cells.PLoSONE5(8):e12358.doi:10.1371/journal.pone.0012358 Editor:RobertE.Means,YaleMedicalSchool,UnitedStatesofAmerica ReceivedApril27,2010;AcceptedJuly28,2010;PublishedAugust23,2010 Copyright:?2