mAFP基因转染树突状细胞免疫对小鼠诱发性肝癌发生的影响  

Effect of mAFP Gene Transfected DC Vaccine on Tumorigenesis of Hepatocellular Carcinoma in Mice

作　　者：匡志鹏[1] 谢裕安[1] 杨帆[1] 罗小玲[1] 梁安民[1] 吴继宁[1] 

机构地区：[1]广西肿瘤防治研究所生物医学研究中心,广西南宁530021

出　　处：《四川肿瘤防治》2007年第2期96-99,共4页Sichuan Journal of Cancer Control

基　　金：国家自然科学基金项目(30360114)

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。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 （pAdBMS-mAFP-DC） ; Group C was inoculated with pAdBMS-mAFP plasmid, and the control goup D is injected with PBS. They were immunized once with 5×10^5 DC（0.1 ml）/mouse administered s.c. in the left flank or 100 nag pAdBMS-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.

关 键 词：树突状细胞 转基因瘤苗 免疫 肝癌 病理形态学 

分 类 号：R735.7[医药卫生—肿瘤]