Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer
OBJECTIVE To investigate the effect and mechanism of picroside Ⅱ on the malignant progression of non-small cell lung cancer(NSCLC).METHODS A549 cells were divided into the control group,picroside Ⅱ low-,medium-and high-concentration groups,K6PC-5[sphingosine kinase 1(SPHK1)activator]group,and picroside Ⅱ high-dose+K6PC-5 group.Cell proliferation,migration and invasion were detected.Besides,the expression of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-2(MMP-2),MMP-9,SPHK1,sphingosine-1-phosphate receptor 3(S1PR3)and extracellular signal-regulated kinase 1/2(ERK1/2)protein in the cells were also observed.BALB/c nude mice were subcutaneously inoculated with A549 cell suspension to establish NSCLC xenograft models.Then they were assigned to the nude mouse-control group,nude mouse-picrosideⅡ low-,medium-and high-dose groups,nude mouse-K6PC-5 group,and nude mouse-picroside Ⅱ high-dose+K6PC-5 group(with 5 mice in each group)to investigate the effect of picroside Ⅱ on their tumor mass and volume.RESULTS Compared with the control group,the OD450 values,EdU-positive cell rates,scratch healing rates,cell invasion number,and the relative expression levels of PCNA,MMP-2,MMP-9,SPHK1,S1PR3 and ERK1/2 protein in the low-,medium-and high-concentration groups of picroside Ⅱ were significantly decreased.Compared with the nude mouse-control group,the tumor mass and volume in the nude mouse-low-,medium-and high-dose groups of picroside Ⅱ were significantly decreased or shrunk.The changes of above indicators were concentration/dose-dependent(P＜0.05).The changing trend of the corresponding indicators in the K6PC-5 group and the nude mouse-K6PC-5 group was opposite(P＜0.05).Compared with the picroside Ⅱ high-concentration group or the nude mice-picroside Ⅱ high-dose group,the above quantitative indicators in the picroside Ⅱ high-concentration+K6PC-5 group cells and the nude mouse-picroside Ⅱ high-dose+K6PC-5 group nude mice were significantly increased or enlarged(P＜0.05).CONCLUSIONS Picroside Ⅱ may inhibit the malignant progression of NSCLC by inhibiting SPHK1/sphingosine-1-phosphate/S1PR3 signaling pathway.
万方数据
维普
