抗肝癌重组免疫毒素对荷人肝癌裸鼠移植瘤生长的抑制作用  

Inhibitory effect of recombinant immunotoxin on human hepatocellular carcinoma xenograft in nude mice

作　　者：付勇[1] 苏雪梅[1] 刘彦仿[2] 赵君[2] 李锴男[2] 杨守京[2] 邹赛英[1] 

机构地区：[1]兰州军区乌鲁木齐总医院病理科,新疆乌鲁木齐830000 [2]第四军医大学基础部病理学教研室,陕西西安710032

出　　处：《中华肿瘤防治杂志》2007年第4期241-244,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30370810)

摘　　要：目的:观察二硫键稳定人源化抗肝癌单链抗体(humanized disulfide stabilization single chain antibody,hdsFv)融合牛蛙核糖核酸酶(rana catesbeiana ribonuclease,RC-RNase)重组免疫毒素(hdsFv-RC-RN-ase)对荷人肝癌裸鼠移植瘤生长的抑制作用。方法:将人肝癌细胞系SMMC-7721细胞接种于裸鼠皮下,建立荷人肝癌裸鼠移植瘤动物模型,随机分为3组,分别经尾静脉注射给予生理盐水、盐酸多柔比星和抗肝癌hdsFv-RC-RNase治疗,疗程为2周。通过测量各实验组裸鼠肿瘤体积及瘤质量变化,绘制肿瘤生长曲线并计算抑瘤率。治疗结束后取各组裸鼠肿瘤组织及重要器官HE染色,光学显微镜下观察。结果:治疗后hdsFv-RC-RNase组与空白对照组相比较,荷人肝癌裸鼠移植瘤生长速度显著减慢,肿瘤体积和瘤质量明显减小,P<0·01;同样,与盐酸多柔比星组相比较差异有统计学意义,P<0·01。hdsFv-RC-RNase组和盐酸多柔比星组抑瘤率分别为(78·9±4·1)%和(70·3±6·6)%,P<0·01。光学显微镜下观察hdsFv-RC-RNase组和盐酸多柔比星组肿瘤组织出现明显坏死,尤以前者更为显著。各实验组裸鼠重要器官未见明显异常。结论:抗肝癌hdsFv-RC-RNase重组免疫毒素对荷人肝癌裸鼠移植瘤生长具有良好的抑制作用。OBJECTIVE： To observe the inhibitory effect of the anti-HCC humanized disulfide stabilization single chain antibody （hdsFv） fusing Rana catesbeiana ribonuclease （RC-RNase） recombinant immunotoxin （hdsFv-RC-RNase） on human hepatocellular carcinoma xenograft in nude mice. METHODS： The xenograft models were established by injecting the hepatocellular carcinoma cell line SMMC-7721 into nude mice. Then they were divided randomly into three groups and injected saline, adriamycin and hdsFv-RC-RNase in each animal through the caudal vein, respectively. The treatment lasted for up to two weeks. The growth curves and the growth inhibitory rate were analyzed by measuring the change of the carcinoma volume and weight of the each group. The xenograft, and important organs were harvested at the end of treatment and the tissues were examined by HE staining and a light microscope. RESULTS： After treatment, Compared with the control group, the growth rate decreased markly in hdsFv-RC-RNase group, so did the xenograft volume and weight, P〈0.01. There was significant difference between the hdsFv-RC-RNase group and saline group, P〈0.01, and so was between the hdsFv-RC-RNase group and adriamycin group, P〈0.01. The inhibitory rate of carcinoma in the hdsFv-RC-RNase group and adriamycin group reached （78.9±4.1）% and （70.3±6.6）%, respectively. On a light microscope, the notable necrosis occurred in the hdsFv-RC- RNase group, which was more obvious than that in the adriamycin group. There were no abnormal changes in important organs of the nude mice. CONCLUSION： The hdsFv-RC-RNase recombinant immunotoxin has a good inhibitory effect on the human hepatocellular carcinoma xenograft in nude mice.

关 键 词：癌 肝细胞/免疫学 肝肿瘤/免疫学 核糖核酸酶类 免疫毒素类 重组 遗传 疾病模型 动物 

分 类 号：R735.7[医药卫生—肿瘤]