Ds-echinoside A,a new triterpene glycoside derived from sea cucumber,exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions  

作　　者：Qin ZHAO Zhi-dong LIU Yong XUE Jing-feng WANG Hui LI Qing-juan TANG Yu-ming WANG Ping DONG Chang-hu XUE 

机构地区：[1]College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2011年第7期534-544,共11页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：Project supported by the National High-Tech R & D Program (863) of China (No. 2007AA091805);and the National Natural Science Foundation of China (Nos. 30972284 and 30871944)

摘　　要：Ds-echinoside A (DSEA),a non-sulfated triterpene glycoside,was isolated from the sea cucumber Pearsonothuria graeffei.In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion,migration,invasion,and angiogenesis.In this study,we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2,with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L,and suppressed Hep G2 cell adhesion,migration,and invasion in a dose-dependent manner.DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo.Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9),which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis.DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1),an important regulator of MMP-9 activation.From the results of Western blotting,the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA.These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.Ds-echinoside A （DSEA）,a non-sulfated triterpene glycoside,was isolated from the sea cucumber Pearsonothuria graeffei.In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion,migration,invasion,and angiogenesis.In this study,we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2,with a half-maximal inhibitory concentration （IC50） of 2.65 μmol/L,and suppressed Hep G2 cell adhesion,migration,and invasion in a dose-dependent manner.DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane （CAM） assay in vivo.Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 （MMP-9）,which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis.DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 （TIMP-1）,an important regulator of MMP-9 activation.From the results of Western blotting,the expressions of nuclear factor-kappa B （NF-κB） and vascular endothelial growth factor （VEGF） were found to be remarkably reduced by DSEA.These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.

关 键 词：Triterpene glycoside Ds-echinoside A (DSEA) Metastasis ANGIOGENESIS Nuclear factor-κB (NF-κB) Matrix metalloproteinase-9 (MMP-9) Vascular endothelial growth factor (VEGF) 

分 类 号：R979.1[医药卫生—药品]