蓖麻毒蛋白A链与抗表皮生长因子受体单克隆抗体偶联物的抗肿瘤效应  

Antitumoral effect of the immunoconjugate composed of ricin A-chain and EGFR mab

作　　者：申苏建[1] 吴金明[1] 金思思[1] 黄智铭[1] 吴建胜[1] 

机构地区：[1]温州医学院附属第一医院消化内科

出　　处：《中国临床药理学与治疗学》2009年第11期1234-1239,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:将蓖麻毒蛋白(ricin)A链(RTA)与表皮生长因子受体(epidermal growth factor receptor,EGFR)mab偶联形成免疫毒素(immunotoxin,IT),并评价该偶联物的体外抗肿瘤作用。方法:从蓖麻籽中提纯RTA,采用N-琥珀酰胺-3-(2-吡啶二硫)丙酸酯[N-succinimidyl-3-(2-pyridyldithio)-pro-pionate,SPDP]为偶联剂制备ITEGFR mab-RTA,以SDS-PAGE检测RTA的提取及IT的偶联,以DAB显色法检测IT对人肝癌HepG2细胞的结合能力,以间接ELISA方法测定IT的免疫反应性,以CCK-8法测定IT的体外抗肿瘤作用。结果:RTA从蓖麻籽中提取后,与EGFR mab成功偶联。IT基本保留了EGFR mab对HepG2细胞的结合能力和免疫反应性,及对HepG2细胞和LO2细胞表现了不同的体外细胞毒作用。结论:EGFR mab-RTA具有特异性抑制肝癌细胞增殖的作用,有望成为新型的抗肝癌药物。AIM： To research the antittunoral effeet in vitro of the immunotoxin composed by RTA and EGFR mab. METHODS： Taking SPDP as the cou- pling agent, RTA, which was purified from castor bean, was linked with EGFR mab. After further purification, the purification of RTA and the construction of the immunotoxin were detected by SDS-PAGE. The combining capacity to HepG2 cells was detected by DAB chromogenic method. The immunoreactivity was detected by indirect ELISA. The cytotoxicity in vitro was detected by CCK-8 method. RESULTS： The immunotoxin was constructed successfully. Immunotoxin retained the combining capacity of EGFR mab to He- pG2 cells and a major part of the immunoreactivity. The immunotoxin displayed a different cytotoxicity between HepG2 cells and LO2 cells. CONCLUSION： Immunotoxin plays a specific role in suppressing the multiplication of the hepatoma carcinoma cell and has a good prospect in liver cancer treatment.

关 键 词：蓖麻毒蛋白A链 单克隆抗体 免疫毒素 

分 类 号：R730.51[医药卫生—肿瘤] R996.2[医药卫生—临床医学]