抗Ⅳ型胶原酶单链抗体scFv (3G11)联合顺铂的抗肿瘤活性

Anticancer Effects of the Single-chain Fv Fragment scFv (3G11) Against Type Ⅳ Collagenase in Combination with Cisplatin

目的研究抗Ⅳ胶原酶基因工程单链抗体scFv (3G11)联合顺铂的抗肿瘤效果。方法明胶酶谱法、Western-blot法研究顺铂对肿瘤细胞分泌Ⅳ胶原酶蛋白的影响,MTT法、实验动物肿瘤模型研究scFv (3G11)与顺铂联合在体外和体内试验中的抗肿瘤效果。结果顺铂可抑制肿瘤细胞分泌的Ⅳ胶原酶活性,scFv (3G11)与顺铂联合在体外试验中可抑制人肝癌BEL-7402细胞的生长,体内试验中对小鼠移植性肝癌H22有显著的抑制作用,药物相互作用指数(CDI值)<1。结论scFv (3G11)和顺铂联合应用对肝癌的治疗有协同作用。

Objective To explore the effect of recombinant scFv （3G11 ） directed against type Ⅳ collagenase in combination with cisplatin on the therapy of hepatocellular carcinoma. Methods The effects of cisplatin on the type Ⅳ collagenase secreted by cancer cells were investigated by gelatin zymography analysis and Western- blot. The antitumor activity of scFv （3G11 ） in combination with cisplatin was evaluated by MTT assay in vitro and a mouse hepatoma 22 model in vivo. Results Cisplatin inhibited the activity of type Ⅳ collagenase. ScFv （3G11 ） in combination with cisplatin showed significant inhibition effects on the growth of hepatocellular carcinoma both in vitro and in vivo. The coefficient of drug interaction （CDI） was less than 1. Conclusions ScFv （3G11） in combination with cisplatin demonstrated synergetic effects on the therapy of hepatocellular carcinoma.