Endostar, a modified recombinant human endostatin, suppresses angiogenesis through inhibition of Wnt

来源 :2016年浙江省医学会心电生理与起搏学术年会 | 被引量 : 0次 | 上传用户:chen6524
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  Endostar,a novelmodified recombinant human endostatin,is nowwidely studied for the treatment of diseases that arecharacterized or caused by pathological angiogenesis.However,its molecular mechanism remains unclear.In this study,we investigated the effects of Endostar on the Wnt/β-catenin signaling pathway,which has emerged as animportant aspect of angiogenesis.We showed that Endostar significantly inhibited the proliferation,migration,invasion,and capillary-like tube formation ofhuman umbilical vascular endothelial cellsin a dose-dependent manner.Using a luciferase reporter assay,we alsodemonstrated that Endostar suppressed β-catenin-dependent Tcell factor transcriptional activityin increasing doses.Moreover,we found that Endostar treatment also restricted the stabilized mutant β-catenin-mediated increase in transcriptional activity,suggesting thatEndostar exerts its inhibitory influence onWnt/β-catenin signalingby targeting β-catenin or its downstream molecules.Western blot and immunofluorescence results revealed that Endostar significantly decreased nuclear and total β-cateninlevels.Finally,we discovered that Endostar down-regulated cyclin D1 and VEGF,two proteins that are known as the downstream targetsof Wnt/β-catenin signaling and that also play important roles inangiogenesis.Our findings suggested thatEndostar suppressed Wnt/β-catenin pathwayactivity in angiogenesis.These resultssupport the use of Endostar in further clinical applications.
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