抗VEGFR-2嵌合Fab抗体对鼠肝癌原位移植瘤及其新生血管的抑制作用  

Inhibitory effects of a chimeric anti-VEGFR-2 Fab antibody on tumor growth and angiogenesis in an orthotopic xenograft mouse model of hepatocellular carcinoma

作　　者：张建民[1] 施晓雷[2] 朱进[3] 吴亚夫[2] 

机构地区：[1]南京医科大学鼓楼临床医学院肝胆外科,江苏省南京市210008 [2]南京大学医学院附属鼓楼医院肝胆外科,江苏省南京市210008 [3]中国人民解放军南京军区军事医学研究所,江苏省南京市210002

出　　处：《世界华人消化杂志》2010年第34期3621-3626,共6页World Chinese Journal of Digestology

基　　金：南京市卫生局医学科技发展基金资助项目;No.ZKX09027~~

摘　　要：目的:探讨鼠源抗VEGFR-2嵌合Fab抗体对小鼠肝癌原位移植瘤的抑制作用及对其肿瘤血管生成的影响.方法:ELISA法检测嵌合Fab抗体的结合活性.直接注射法建立小鼠H22肝癌原位移植瘤模型,造模成功小鼠随机分为生理盐水空白对照组和cFab组,每组24只.观察用药前后小鼠体质量变化、生存时间及肿瘤组织病理形态变化,免疫组织化学检测肿瘤组织内微血管密度(MVD).结果:嵌合Fab抗体与VEGFR-2有较高的亲和力.cFab组肝脏肿瘤体积显著小于生理盐水组(313.9mm3±41.9mm3vs635.4mm3±70.1mm3,P<0.05);两组间小鼠中位数生存时间有显著性差异(20.0d vs13.0d,χ2=4.611,P=0.032);cFab组肝脏实体瘤内MVD较生理盐水组显著性减少(34.48±1.39vs9.56±1.26,P<0.05).结论:鼠源抗VEGFR-2Fab抗体通过抑制肿瘤新生血管形成,从而抑制小鼠肝癌原位移植瘤的生长.AIM：To investigate the inhibitory effects of a mouse chimeric anti-VEGFR-2 Fab antibody on tu-mor growth and angiogenesis in an orthotopic xe-nograft mouse model of hepatocellular carcinoma.METHODS：The antigen-binding activity of cFab antibody was assessed by ELISA.An orthotopic xenograft mouse model of hepatocellular carci-noma was created by direct injection of H22 cells into the liver parenchyma of ICR mice.Twenty-four ICR mice bearing orthotopic HCC were divided into two groups：control group（treated with normal saline）and cFab group（treated with cFab antibody）.After the treatment,tumor weight and mouse survival time were compared between the two groups.Histological changes and microvessel density（MVD）in tumors were also evaluated.RESULTS：The chimeric anti-VEGFR-2 Fab antibody exhibited a strong binding activity to VEGFR-2.Tumor size in the cFab group was significantly decreased compared with the con-trol group（313.9 mm 3 ±41.9 mm 3 vs 635.4 mm 3 ±70.1 mm 3,P0.05）;and the mice of the cFab group had a significantly longer survival time（20.0 d vs 13.0 d,Long-rank testχ2=4.611,P= 0.032）.The MVD in the cFab group was also sig-nificantly lower than that in the control group（34.48±1.39 vs 9.56±1.26,P0.05）.CONCLUSION：The chimeric anti-VEGFR-2 Fab antibody can inhibit tumor growth in an ortho-topic xenograft mouse model of hepatocellular car-cinoma possibly by inhibiting tumor angiogenesis.

关 键 词：肝细胞癌 嵌合Fab抗体 血管内皮生长因子受体2 肝移植 动物模型 

分 类 号：R735.7[医药卫生—肿瘤]