Alphastatin多肽对胶质瘤血管生成拟态的抑制作用及其相关机制  

The effection and the mechanism of alphastatin supressing the vasculogenic mimicry formation of glioma

作　　者：郭世文[1] 张熙[1] 尉春艳[2] 

机构地区：[1]西安交通大学医学院第一附属医院神经外科,西安710061 [2]西安交通大学医学院第二附属医院妇产科,西安710004

出　　处：《重庆医学》2011年第21期2084-2086,共3页Chongqing medicine

基　　金：国家自然科学基金资助项目(30672126)

摘　　要：目的探讨24肽Alphastatin对胶质瘤血管生成拟态的抑制作用及其相关机制。方法应用MTT、Transwell法、细胞三维培养和Western blot等方法检测Alphastatin对SHG44细胞增殖、迁移和血管形成能力的抑制作用及血管内皮生长因子(VEGF)、上皮细胞激酶(EphA2)、基质金属蛋白酶2(MMP2)蛋白的表达。结果对照组细胞迁移数为178.71±18.81,实验组(100 nmol/L,1 000 nmol/L,10 000 nmol/L)细胞数目分别为142.57±12.12,92.71±17.68和30.00±7.72,对照组细胞数显著高于实验组(P<0.01);对照组拟态血管数目为56.80±12.21,也显著高于实验组(47.71±10.58,18.86±8.40,8.43±5.62),P<0.01。Alphastatin虽然能作用于VEGF通路,却不能直接抑制VEGF蛋白的表达,但是可明显抑制EphA2蛋白的磷酸化和MMP2蛋白的活化,减少血管生成拟态的形成。结论 Alphastatin不但可抑制肿瘤血管内皮细胞依赖性血管,还能抑制血管生成拟态,可能是理想的肿瘤血管抑制肽。Objective To investigate the effection and the mechanism of alphastatin supressing the vasculogenic mimicry formation of glioma.Methods MTT,transwell and three-dimentional culture were used to detect the proliferation,migration and tubule formation of SHG44.The expression of VEGF,EphA2 and MMP2 was detected by western blot.Results The number of cell migration in control group was 178.71±18.81,significantly higher than that in experimental group（142.57±12.12,92.71±17.68,30.00±7.72）（P〈0.01）.The number of vasculogenic mimicry was 56.80±12.21,also significantly higher than that in experimental group（47.71±10.58,18.86±8.40,8.43±5.62）（P〈0.01）.In experimental group the phosphorylation of EphA2 protein and activation of MMP2 protein were much supressed by alphastatin and there was no change in VEGF protein.Conclusion Alphastatin can supress not only endothelial cell dependent blood vessel but also vasculogenic mimicry.It may be a ideal vasoinhibitory peptide.

关 键 词：血管生成拟态 Alphastatin多肽 增殖 迁移 血管形成 

分 类 号：R739.41[医药卫生—肿瘤]