多聚物PVP介导免疫基因B7-H3治疗小鼠肝癌的实验探讨

PVP-mediated B7-H3 immunogene therapy for hepatocellular carcinoma in the mouse model

目的:探讨B 7-H 3基因对肝癌的治疗作用及其作用机制。方法:皮下种植法建立肿瘤模型,以聚乙烯吡咯烷酮(PVP)为载体,对荷肝癌小鼠行瘤体内注射携带B 7-H 3基因的真核表达质粒pcDNA 3.1(+)-m B 7-H 3,检测治疗后小鼠体内m B 7-H 3基因的表达、小鼠血清中IFN-γ表达量、脾脏的细胞毒性T淋巴细胞(cytotox ic tlym phoctye,CTL)活性、肿瘤的大小、肿瘤局部的淋巴细胞浸润情况及荷瘤小鼠的生存期。结果:经m B 7-H 3基因治疗后,治疗组小鼠血清中IFN-γ表达量和脾脏的CTL活性明显增强(P<0.01),肿瘤局部淋巴细胞浸润明显,肿瘤生长受到抑制,荷瘤小鼠的存活期明显延长。结论:B 7-H 3基因有效地调动宿主抗肝癌的免疫反应。

Objective： To study the PVP--mediated B7--H3 immunogene therapy for hepatocellular carcinoma in the mouse model. Methods：Tumors were established subcutaneosly in mouse, and received injection with expressing pcDNA3. 1-- Flag -- mB7 -- H3 with PVP as carrier, and their growth were monitored. Expression of mB7--H3 was detected by immunohistochemistry and Western blotting. The CTL activity and the serum level of IFN-γ were also evaluated. The histological changes of the tumor and the tumor volume in tumor bearing mice were tested after gene therapy. Results：The serum IFN -γ level and the CTL activity were increased significantly after gene therapy （P〈0.05）. The growth suppression of the established tumors and the protective lymphocytes accumulation were found in local tumor. Gene therapy significantly prolonged the survival of tumor bearing mice. Conclusion ：Experimental B7--H3 gene therapy improves the positive immune reaction of host mice against the inoculated hepatocellular carcinoma.