Angiostatin作用靶点的初步研究  

Target of Angiostatin

作　　者：陶永辉[1] 张莲芬[1] 金坚[1] 

机构地区：[1]江南大学工业生物技术教育部重点实验室.江南大学生物工程学院生物制药系,江苏无锡214036

出　　处：《中国药理学通报》2006年第9期1084-1088,共5页Chinese Pharmacological Bulletin

基　　金：江苏省自然科学基金资助项目(NoBK2002071)

摘　　要：目的研究血管抑素对血管内皮细胞作用的靶点。方法以99Tcm-重组人血管抑素、FITC-重组人血管抑素和FITC-重组人血管抑素抗体为示踪分子,进行小鼠S180肿瘤模型显像、Matrigel血管模型放射自显影和HMEC-1细胞的流式细胞术。采用亲和甑别技术对重组人血管抑素结合分子实施了分离,MS测序,并与蛋白质数据库进行了比较。结果99Tcm-重组人血管抑素可聚集在S180肿瘤部份,其特异地识别部位为新生血管。流式细胞术提示HMEC-1细胞表面存在重组人血管抑素的结合位点,亲和甑别发现3种结合蛋白,其中预测分子tubulin是重要的肿瘤药物靶点。结论血管抑素的作用靶点是特异靶向新生血管内皮细胞的,且其作用可能是多因素的。Aim To investigate the specificity of angiostatin to vascular endothelial cells. Methods S180 tumor imaging and autoradiography of angiogenesis on Matrigel model was developed with ^99Tc^m-recombinant human angiostatin （^99Tc^m-rhAS） as a tracer, and FCM on human mierovaseular endothelial cell-1 （HMEC-1） with FITC-rhAS or rhAS antibody. The binding protein of rhAS on HMEC-1 was isolated by affinity chromatography, and the proteins was sequenced with MS. Results ^99Tc^m-rhAS was concentrated on the tumor site in vivo, and the rhAS was specific to angiogenesis of tumor. There were some binding sites on the surface of HMEC-1. Three proteins which are able to bind rhAS were obtained by affinity chromatography, among which tubulin sequenced was an important target for tumor. Conclusion The angiostatin is specific to novel vascular endothelial cell, and its mechanism targeting tumor is complicated.

关 键 词：血管抑素 人微血管内皮细胞 结合蛋白 

分 类 号：R-332[医药卫生] R322.12