重组腺病毒介导人野生型p53和B7-1基因诱导喉癌细胞凋亡并增强其免疫原性  

Adenovirus-mediated co-transfer of human wild-type p53 and B7-1genes induces apoptosis and enhances immunogenicity in laryngocarcinoma cells

作　　者：邱兆华[1] 潘鲁浙[1] 劳妙芬[1] 吴祖泽[1] 

机构地区：[1]北京放射医学研究所,北京100850

出　　处：《生物技术通讯》2002年第1期1-5,共5页Letters in Biotechnology

基　　金：美国百特医疗用品公司资助~~

摘　　要：为开展喉癌的复合基因治疗,观察共表达人野生型p53和B7-1基因的重组腺病毒Ad-p53/B7-1对喉癌细胞增殖及免疫原性的影响。检测到Ad-p53/B7-1介导的人野生型p53基因可抑制喉癌细胞增殖并诱导其凋亡,同时B7-1基因的导入可增强喉癌细胞的免疫原性基因修饰的癌细胞可刺激自体肿瘤浸润淋巴细胞增殖,并诱导外周血淋巴细胞形成对肿瘤具有特异杀伤性的细胞毒性T淋巴细胞。Co-transferof immunomodulatoryandantiproliferativegenesmay be thebasisfor new strategiesto potentiate tumorregression.The purposeof thisstudywas to developa combinationgenetherapystrategyfor the treatmentof laryngocarcinoma.Hep-2cellswereinfectedwithAd-p53/B7-1(Adenoviralvectorco-exressinghumanwild-typep53and B7-1proteins),Ad-p53(Adenoviralvectorexpressinghumanwild-typep53proteins)andAd-GFP(Adenoviralvector expressinggreenfluorescenceprotein).Growthrateof infectedHep-2cellswas determinedby cellcountassay.The3'ends of theapoptoticDNAfragmentsinducedby transferredp53geneproductweredetectedin Hep-2cellsby TdTassay.The effectof transferredB7-1geneon theimmunogenicityof laryngocarcinomacellswas evaluatedby mixedlymphocytesand tumorcellsreaction(MLTR)andcytotoxicityassay.By theintroductionof wild-typep53gene,thegrowthof Hep-2cells was inhibitedandtheirapoptosiswas induced.By theintroductionof B7-1gene,theimmunogenicityof laryngocarcinoma cellswas increased.Significantproliferationof tumorinfiltratinglymphocytes(TILs)andtumor-specificcytotoxicityof cytotoxicT lymphocytes(CTLs)wereinducedby B7-1costimulationin vitro.Theresultssuggestthattheco-transferof humanwild-typep53and B7-1genesintotumorcellsvia recombinantadenovirusmay be furtherdevelopedintoan effectiveandpracticalcombinationgenetherapystrategyforlaryngocarcinoma.

关 键 词：重组腺病毒 抑癌基因 p53 免疫共刺激分子B7-1 喉癌 复合基因治疗 癌细胞凋亡 免疫原性 

分 类 号：R739.65[医药卫生—肿瘤]