新型靶向性药物VEGF-hFc的抗肿瘤研究  

Anticancer activities of a new targeting drug VEGF-hFc

作　　者：邹利平[1] 栾广信[1] 俸婷婷[1] 徐弈江[1] 吴传芳[1] 

机构地区：[1]四川大学生命科学学院功能基因组实验室,成都610064

出　　处：《四川大学学报（自然科学版）》2011年第4期929-934,共6页Journal of Sichuan University(Natural Science Edition)

基　　金：国家自然科学基金重大研究计划(90919005)

摘　　要：生物机体内天然存在许多受体与配体,它们之间亲和结合力远远高于抗体亲和力(K_d=10^(-8)～10^(-9)).本实验根据VEGFR和VEGF之间的高亲和力(K_d=1.6×10^(-11)),以新生血管细胞表面的VEGFR为靶点,设计VEGF-hFc融合蛋白作为靶向抗肿瘤药物.在本实验中构建pcDNA3.1-IgG leader-VEGF-hFc重组载体,转染CHO/dhFr^-细胞真核表达融合蛋白VEGF-hFc,并通过Protein A纯化.使用A549细胞构建人非小细胞肺癌裸鼠肿瘤模型,小鼠静脉注射10μg VEGF-hFc融合蛋白用以抗肿瘤研究.连续给药4次后,肿瘤生长曲线表明,与对照组相比,实验组小鼠的肿瘤生长得到明显的抑制甚至消退;数据统计显示,VEGF-hFc肿瘤抑制率达90%.There are lots of endogenous ligands and receptors, such as VEGF and VEGFR,whose affinity （Ka = 1.6 × 10^-11） is about 100 folds higher than that of antibody drugs （Ka = 10^-8-10^-9 ）. Based on the high affinity of between VEGFR and VEGF, a fusion protein VEGF-hFc was designed to target new blood vessel cells expressing VEGFR. In this research, a pcDNA3.1-IgG leader-VEGF-hFc eukaryotic expression vector was constructed and transfected into CHO/dhFr- cells. Fusion proteins were secreted by CHO/dhFr^- cells, followed by affinity purification. Homo non-small-cell lung carcinoma SCID mouse tumor model was constructed with A549 cells. To study the ability of this fusion protein to suppress tumor growth, mouse veins were injected with 10μg fusion proteins. After 4 administrations, compared with the control group, the growth curve of tumor suggests that the tumor of experimental group mouse was suppressed, and in some cases even eliminated. These data showed that VEGF-hFc can suppress tumor growth up to 90 %.

关 键 词：VEGF VEGFR HFC VEGF_hFc 靶向性 肿瘤抑制 

分 类 号：Q789[生物学—分子生物学]