Anti-angiogenetic effect of recombinant human p43 and its mechanism

The purpose of this study was to investigate the effects and mechanism of recombinant human p43 (YS-1) on angiogenesis，and explore the antitumor activity of YS-1 in nude mice xenografted with lung adenocarcinoma A-549.Endothelial cell proliferation assay,cell migration assay,tube formation assay,rat aortic ring assay and chicken chorioallantoic membrane(CAM) assay were used to evaluate the anti-angiogenetic activity of YS-1,and Western blot analysis was used to investigate the related mechanism.A model of lung adenocarcinoma A-549 xenograft in nude mice was used to explore the antitumor efficacy of YS-1.It was found that YS-1 inhibited endothelial cell migration and tube formation,and YS-1 obviously inhibited microvessel sprouting from rat aortic rings and the vessel growth in CAM.In addition,YS-1 attenuated the activation of VEGFR2,MEK1/2 and Akt in response to vascular endothelial growth factor (VEGF).Moreover,high dose of YS-1(10mg/kg) was shown to exert a remarkable antitumor effect in the examined model.Therefore,YS-1 can inhibit adenocarcinoma A-549 xenograft in nude mice and its mechanism may be related to the inhibition of angiogenesis resulting from the attenuation of activated VEGFR2 and downstream signaling molecules.