干细胞样U87胶质瘤细胞向内皮细胞转分化及VEGFR2人源化单克隆抗体的干预作用  

Stem cell-like U87 cells trans-differentiating into endothelial cells and inhibition of anti-VEGFR2 human monoclonal antibody

作　　者：宣自学 张琦[2] 李琳娜[2] 原野 徐诚望[2] 杨德宣[2] 王珊珊[2] 袁守军[2] 

机构地区：[1]浙江省人民医院药学部,浙江杭州310014 [2]军事医学科学院放射与辐射医学研究所药理毒理研究室,北京100850 [3]山东步长神州制药有限公司,山东菏泽274000

出　　处：《中国药理学通报》2015年第3期339-345,共7页Chinese Pharmacological Bulletin

基　　金：国家科技重大专项-综合性新药研究开发技术大平台资助项目(No 2012ZX09301003-001)

摘　　要：目的建立干细胞样U87胶质瘤细胞向内皮细胞的转分化模型,初步评价抗VEGFR2人源化单克隆抗体对转分化的影响。方法体外诱导培养获得干细胞样U87胶质瘤细胞;流式细胞仪检测CD133+细胞含量;定量PCR检测CD133、Nestin以及VEGFR2表达;观察干细胞样U87细胞的致瘤能力、肿瘤生长速度和CD31表达情况;观察干细胞样U87细胞在Matrigel上血管状结构形成和CD31、CD34、vW F表达情况;建立干细胞样U87细胞向内皮细胞的转分化模型,评价抗VEGFR2人源单抗对转分化的抑制作用。结果获得干细胞球样的U87细胞,其肿瘤生长更快,且血管增多,接种在Matrigel上形成血管状结构,CD31、CD34、vW F表达增加;抗VEGFR2人源单抗使血管状结构和CD31、CD34、vW F表达均减少。结论成功建立干细胞样U8细胞向内皮细胞转分化模型,VEGFR2人源化单抗对转分化有抑制作用。Aim To establish the trans-differentiation model of stem cell-like U87 glioma cells into endotheli-al cells, and evaluate the effect of anti-VEGFR2 hu-man monoclonal antibody on this process. Methods To obtain stem-like cells from U87 cell line, U87 tumor spheres were induced in vitro, then they were i-dentified by FACS and qPCR, and the tumorigenicity, tumor growth and CD31 vascular density were also de-tected. Finally, we established the trans-differentiation model to evaluate the effect of anti-VEGFR2 fully hu-man monoclonal antibody. Results Big tumorspheres were formed successfully, an obvious increase of the CD133＋ cells was showed by FACS analysis, and the up-regulation of CD133 , Nestin and VEGFR2 was fur-ther revealed by qPCR assay. Additionally, tumors from stem-like U87 cells grew faster, and the blood

关 键 词：干细胞样U87细胞 Matrigel胶 内皮细胞 转分化 VEGFR2 血管状结构 

分 类 号：R322.12[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]