【作者】 赵芹； 薛勇； 王静凤； 李辉； 唐庆娟； 王玉明； 董平； 薛长湖；

【Author】 Qin Zhao,Yong Xue,Jing-feng Wang~*,Hui Li,Qing-juan Tang,Yu-ming Wang,Ping Dong,Chang-hu Xue* College of Food Science and Engineering,Ocean University of China,Qingdao,Shandong Province,266003,China.

【机构】 中国海洋大学食品科学与工程学院；

【摘要】 目的革皮氏海参皂苷Ds-echinosideA(DSEA)为首次从自然界中分离得到的三萜皂苷,本文研究了其抗肿瘤细胞转移活性及其作用机制。方法采用MTT法检测不同剂量DSEA对肿瘤细胞和内皮细胞增殖的影响;采用细胞粘附实验、划痕法和Transwell小室法研究了DSEA对肿瘤细胞粘附、迁移和侵袭能力的影响;采用体外小管形成实验和鸡胚绒毛尿囊膜(CAM)血管新生模型,观察DSEA对血管新生的影响。采用免疫细胞化学以及Western-blotting法对EA抗肿瘤转移的机制进行了探讨。结果 EA具有抑制肿瘤细胞和内皮细胞增殖的活性,可显著抑制肿瘤细胞的迁移、侵袭、粘附能力,下调MMP-9的表达,提高TIMP-1的表达,下调VEGF和NF-κB的表达。结论海参皂苷具有显著的抑制肿瘤转移的作用,其作用机制可能是通过调节NF-κB信号通路,并进一步调控其下游的MMP-9和VEGF的蛋白表达实现。更多还原

【Abstract】 Objectives Ds-echinoside A（DSEA）,a non-sulfated triterpene glycoside obtained from the natural world for the first time,was isolated from the sea cucumber,Pearsonothuria graeffei.The effects of DSEA on anti-metastatic,anti-angiogenic and the factors involved in these processes were assessed.Methods In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion,migration, invasion,and angiogenesis.Results In this study,we found that DSEA inhibited the proliferation of HepG2 tumor cells,with an average IC₅₀ value of 2.65μM,and suppressed HepG2 cell adhesion,migration,and invasion in a dose-dependent manner.DSEA also obviously reduced tube formation of human endothelial cells（ECV304） 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 angiogenesis and tumor metastasis.DSEA also increased the expression level of tissue inhibitor of metalloproteinase-1（TIMP-1）,an important regulator of MMP-9 activation.From the results of western blotting,the expression of nuclear factor-kappa B（NF-kB） and vascular endothelial growth factor（VEGF） were found to be remarkably reduced by DSEA.Conclusion These findings suggest that DSEA exhibits significant anti-metastatic activity through specific inhibition of NF-κB-dependent MMP-9 and VEGF expression.更多还原