Aurora Kinase Inhibitor VX-680 Suppresses The Proliferation And Migration Of HUVECs As Well As Angiogenesis

Objective:1.To investigate the effects of VX-680 on the proliferation,apoptosis,migration as well as angiogenesis of HUVECs.2.To explore the molecular mechanism of VX-680 affecting the angiogenesis of HUVECs.Methods:1.To detect the change of proliferation,apoptosis,adhesion,migration as well as tubular formation of HUVECs handled with different concentrations(0 ?M,1.5 ?M,2.25?M)of VX-680 by MTT assay,plate clone formation assay,DAPI staining,wound healing assay,tubular formation assay as well as chicken embryo chorioallantoic membrane assay.2.Western blot got used to observe that the expression of the apoptosis molecules(Caspase-3 and PARP),vascular endothelial growth factor(VEGF)as well as signal pathway related protein AKT / p-AKT expression.Results:1.After HUVECs were handled with different concentration of VX-680,the results of MTT assay demonstrated that the proliferation rate of HUVECs gradually decreased with the increase of VX-680 concentration compared with the control group.The results of plate clone formation assay demonstrated that the colony formation rate of HUVECs gradually decreased with the increase of VX-680 concentration.DAPI staining got used to observe the proportion of nuclear condensation as well as nuclear fragmentation of HUVECs in the experimental group increased compared with the control group.Theresults of wound healing assay demonstrated that the apoptosis rate increased gradually with the increase of the VX-680 concentration compared with the control group.The results of tubular formation assay as well as chicken embryo chorioallantoic membrane assay demonstrated that the angiogenesis number of HUVECs gradually decreased with the increase of VX-680 concentration.2.The results of western blot demonstrated that with the increase of VX-680 concentration,the expression level of procaspase-3 as well as PARP remarkably decreased,the expression of cleaved-PAPR increased,and the expression of VEGF expression as well as p-AKT protein both decreased,while the total protein AKT had not changed remarkably.Conclusions:1.VX-680 can inhibit proliferation,migration as well as tubule formation of HUVECs,while promote apoptosis of HUVECs in a concentration manner.2.VX-680 can remarkably promote the apoptosis of HUVECs by regulating the activity of Caspase-3 as well as PARP.VX-680 can remarkably reduce the angiogenic ability of HUVECs by down-regulating the expression of VEGF as well as inhibiting the AKT signaling pathways.Objective:To investigate the effects of Verteporfin(VP)on proliferation,apoptosis,adhesion as well as migration of esophageal squamous cell carcinoma cell KYSE150.Methods:KYSE150 cells were handled with VP at various concentrations(0 ?M,0.15 ?M,0.3?M)for 24 h respectively,and then the cells were observed for morphological change under an inverted microscope.The effects of VP on KYSE150 cells proliferation was assessed by CCK8.Apoptosis was detected by DAPI staining.The cell-cell adhesion was determined by cell slow aggregation assay as well as cell separation assay separately.Wound healing assay were applied to evaluate the capacity of cell migration.Results:Compared with the control group,cells handled with VP became smaller and rounder,some cells floated with the increase of VP concentration.The results of the CCK-8experiment demonstrated that cell proliferation rate gradually decreased in a concentrationand time-dependent manner of VP(P<0.05);The DAPI staining demonstrated that cells handled with VP became nuclear concentration or nuclear fragmentation,and the number of apoptosis gradually increased(P<0.01).Both cell slow aggregation assay and cell separation assay demonstrated that cell masses decreased,volume increased as well as density increased(P<0.01);The results of wound healing assay demonstrated that cell migration ability gradually weakened when cells were handled with VP(P<0.01).Conclusions:VP can remarkably inhibit the proliferation as well as migration of KYSE150 cells,and promote the apoptosis as well as adhesion of KYSE150 cells,suggesting VP maybe a novel therapeutic agent for esophageal squamous cell carcinoma.