【摘要】 目的:探讨用mAFP基因转染的树突状细胞(dendritic cells,DC)瘤苗免疫对小鼠诱发性肝癌发生的影响。方法:诱导、扩增C57BL/6J小鼠DC。将表达小鼠AFP基因(mAFP)的重组腺病毒转染DC。80只C57BL/6J雄性小鼠随机分为A、B、C、D组,每组20只。以单纯DC为A组;将表达mAFP基因的重组腺病毒转染DC(pAd-BM5-mAFP-DCs)为B组;表达mAFP基因的质粒DNA(pAdBM5-mAFP)为C组;以单纯PBS(磷酸缓冲液)注射为对照组D组。免疫方法:实验组在每只小鼠的左胁部注射5×105个细胞(0.1ml/次),连续免疫3天,以后每7天接种疫苗1次,继续免疫4次。正常对照组,仅注射0.1ml PBS。在接种免疫的同时,给以二乙基亚硝胺(DEN)、四氯化碳(CCl4)和乙醇联合诱癌。诱癌20周后处死小鼠,检查成瘤情况。同时对肝脏标本进行组织病理学检查。结果:80只免疫小鼠中,A组肝细胞癌发生率为70%;B组肝细胞癌发生率仅为25%;C组肝癌发生率为65%;D组肝癌发生率为75%。B组与其它对照组比较有显著性差异(p<0.05),其他各组比较无显著性意义。结论:转基因pAdBM5-mAFP-DC瘤苗免疫自然诱癌的C57BL/6J小鼠,能激发较强的抗肿瘤免疫反应,降低肝癌的发生率。更多还原

【Abstract】 Objective: To observe the effect of mAFP gene transfected DC vaccine on tumorigenesis of hepatocellular carcinoma in mice.Methods: DC was induced and augmented by recombinant murine IL-4(rmIL-4) and recombinant GM-CSF(rmGM-CSF),and transfected by recombinant adenovirus engineered with mAFP gene.80 C57BL/6J male mice were randomly divided into group A,B,C,and D(20 mice per group).Group A was inoculated with simple DC;Group B was inoculated with DC transduced by mAFP gene(pAdBM5-mAFP-DC);Group C was inoculated with pAdBM5-mAFP plasmid,and the control goup D is injected with PBS.They were immunized once with 5×105 DC(0.1ml)/mouse administered s.c.in the left flank or 100 mg pAdBM5-mAFP plasmid/mouse administered i.m.in the left anterior tibialis muscle.Inoculation once a week for 4 weeks after 3 times of consecutive immunization initially.At the same time of immunization,DEN/CCl4/ethanol was given to induce hepatocellular carcinoma.Tumor incidence was assessed after 20 weeks.Results: After 20 weeks’ induction,the incidence of primary hepatocellular carcinoma(HCC) was 70% in group A;25% in group B;65% in group C; and 75% in group D.There were significant differences between group B compared and other groups(P<0.05),there were no statistics significances for comparison among group A,group C and group D.Conclusion: mAFP transgenic DC tumor vaccine inoculation could induce stronger immunoprotection effects on HCC with AFP-secreted and decrease HCC incidence during primary liver cancer natural occurrence induced by DEN/CCl4/ethanol.更多还原