人原发性肝癌基因的实验研究───肿瘤坏死因子基因的初步应用  

PRELIMINARY STUDIES ON THE EFFECTS OF TUMOR NECROSIS FACTOR GENE TRANSFER ON THE GROWTH OF HUMAN HEPATOCELLULAR CARCINOMA CELLS IN NUDE MICE

作　　者：冯学胜[1] 汤钊猷[1] 郑仲承[1] 王立群[1] 戈凯[1] 薛琼[1] 刘康达[1] 叶胜龙[1] 孙瑞霞[1] 刘新垣[1] 

机构地区：[1]上海医科大学肝癌研究所,中国科学院上海生物化学研究所

出　　处：《中华肿瘤杂志》1995年第3期167-169,共3页Chinese Journal of Oncology

基　　金：美国中华医学基金;中国863基金

摘　　要：将含人肿瘤坏死因子（ＴＮＦα）ｃＤＮＡ的不同逆转录病毒载体（ＬＮＳ－ｔｎｆα、Ｌ－ｔｎｆαＳＮ及ＬＮＣ－ｔｎｆα）和质粒型真核细胞载体（ｐＳＶＫ３－ｔｎｆα），分别用磷酸钙法导入肝癌细胞ＳＭＭＣ－７７２１中，观察ＴＮＦ的表达水平。结果：重组质粒型表达载体ｐＳＶＫ３－ｔｎｆα表达好，２４小时开始分泌ＴＮＦα（５０Ｕ／ｍｌ），４８～７２小时达最高值（９０Ｕ／ｍｌ），９６小时后下降（４０Ｕ／ｍｌ）。将ｐＳＶＫ３－ｔｎｆα重组ＤＮＡ用磷酸钙包裹后直接进行瘤内注射，发现裸鼠外周血ＴＮＦα水平有一过性增高，３周后测量瘤体大小，发现实验组的肿瘤体积明显小于对照组（２．５±１．６ｃｍ比３．２±１．８ｃｍ，ｎ＝６，Ｐ＜０．０５），实验组荷瘤裸鼠的生存时间亦明显延长（４４．０±３．３ｄ比２８．２±２．０ｄ，ｎ＝６，Ｐ＜０．０１）。结果表明，应用ＴＮＦα基因转移进行肝癌的基因治疗是一条值得探索的途径。Abstract An eukaryotic expression vector containing tumor necrosis factor alpha(TNFα ) gene(pSVK3-tnf) was transduced into hepatocellular carcinoma(HCC) cell line , SMMC7721 ,by cal-cium phosphate coprecipation method.The TNF-gene-transduced SMMC7721 cell began to se-crete TNF after 24h(50U/ml),reached peak level at 48～ 72h(90U/ml), and declined after 96h(40U/ml). Three weeks after the pSVK3-tnf DNA entrapped with calcium phosphate was intro-duced directly into subcutaneous nodules of human HCC in nude mice(treated mice) , the growthof HCC was significantly delayed as compared to the pSVK3 group(control mice)(2.5±1.6cmvs.3.2±1.8cm,n=6,P<05 ). There was a transient increase in TNFα level in peripheralblood in the treated but not in the control mice. The survival time of the treated mice wasmarkedly prolonged as compared to the control(44.0±3.3d vs, 28.2±2.0d,n=6,P<0.01).The above results suggest that TNFα gene transfer might be a hopeful therapy for HCC.

关 键 词：肝肿瘤 肿瘤坏死因子 基因治疗 

分 类 号：R735.705[医药卫生—肿瘤]