摘要
目的从美国肉参(Isostichopus badionotus)中分离纯化岩藻糖基化海参硫酸软骨素(sea cucumber chondroitin sulfate,SC-CHS),体外研究其对肿瘤诱导血管生成的抑制作用。方法采用MTT法检测SC-CHS对95D细胞增殖活性的影响;小管形成实验研究SC-CHS对脐静脉内皮细胞(HUVEC)小管形成能力的抑制作用;采用鸡胚尿囊膜(CAM)新生血管模型,研究其对血管生成的影响;通过RT-PCR和WesternBlot法检测其对肿瘤诱导血管生成相关因子缺氧诱导因子(hypoxia inducible factor-1α,Hif-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA和蛋白的表达。结果结果显示SC-CHS能显著抑制95D细胞的增殖,能抑制HUVEC的小管形成作用和CAM血管新生。RT-PCR和Western Blot检测结果表明,高剂量SC-CHS能显著降低95D细胞中Hif-1α和VEGF mRNA的表达,减少VEGF蛋白的合成。结论SC-CHS体外能显著抑制肿瘤血管生成,这可能是通过影响肿瘤细胞中VEGF的合成发挥作用。
Objective To observe the antiangiogenesis effect of chondroitin sulfate(SC-CHS)isolated from Isostichopus badionotus,one of the bioactive compositions of sea cucumber body well,with various biological activities.Methods After being treated with different-concentrations of SC-CHS at different-time,the proliferation of 95D cells was assessed by MTT assay.Inhibition of angiogenesis was assessed by using tube-formation assays in SC-CHS treated HUVEC cells.CAM assays were used to assess inhibition effect of SC-CHS on physiological angiogenesis.The expressions of HIF-1α and VEGF mRNA were detected by RT-PCR,and VEGF protein was detected by Western Blot.Results SC-CHS could inhibit the proliferation of 95D cell,and could inhibit the tube formation as well as decrease the blood vessel growth on the chicken chorioallantoic membrane.SC-CHS could significantly down-regulate the expression levels of HIF-1α and VEGF mRNA when compared with control.The VEGF protein was also decreased.Conclusion SC-CHS exerted significant anti-angiogenic activities owing to their chemical structures and its mechanism is probably to inhibit the proliferation of 95D cells and reduce the expression of VGEF.
出处
《中国海洋药物》
CAS
CSCD
北大核心
2012年第4期14-19,共6页
Chinese Journal of Marine Drugs
基金
国家自然科学基金(No.30871944)
海洋公益性行业科研专项(No.201105029)
国际科技合作项目(No.2010DFA31330)
"泰山学者"建设工程专项经费
关键词
海参
硫酸软骨素
抗肿瘤
小管形成
缺氧诱导因子
血管内皮生长因子
sea cucumber
chondroitin sulfate
anti-tumor activity
tube-formation
hypoxia induciblefactor-1α
vascular endothelial growth factor