重组腺相关病毒介导抑癌基因联合诱导人肝癌细胞系凋亡与生长抑制研究  

The in vitro and in vivo effect of adeno-associated virus-mediated combined p53,p16 and p21 gene transfection on human hepatic carcinoma cell lines

作　　者：张佑彬[1] 冷希圣[1] 彭吉润[1] 吕建峰[1] 翁山耕[1] 王申五[1] 杜如昱[1] 

机构地区：[1]北京大学人民医院肝胆外科,100044

出　　处：《中华普通外科杂志》2002年第5期284-286,共3页Chinese Journal of General Surgery

摘　　要：目的观察腺相关病毒介导的抑癌基因p5 3,p16和p2 1联合治疗肝癌的可能性和效果。方法用携带人野生型p5 3,p16和p2 1的腺相关病毒分别或联合转导人肝癌细胞系HLE ,HepG2 ,QGY 770 1,QGY 770 3,BEL 74 0 2 ,SMMC 772 1,通过体外及裸鼠体内实验研究转基因的表达及对癌的促凋亡和生长抑制作用。结果腺相关病毒介导的p5 3,p16及p2 1对人肝细胞肝癌细胞系均有明显的促凋亡作用 ,体外凋亡率约 30 %左右 ,体内生长抑制率 30 %～ 4 4 % ;联合感染肝癌细胞效果更明显 ,体外凋亡率达 5 6 % ,体内癌生长抑制率 6 5 %。结论腺相关病毒介导的外源抑癌基因p5 3,p16和p2 1不仅对多种肝癌细胞系均有诱导凋亡和抑制生长作用 ,联合应用治疗肝癌更具有明显的相互协同作用。ObjectiveTo evaluate the effect of combined gene transfection with p53,p16 and p21 on the growth of human liver cancer cell lines.MethodsAfter transducing adeno associated virus(AAV) mediated p53, p16 or/and p21 genes to human hepatic carcinoma cell lines HLE,HepG2,QGY 7701,QGY 7703,BEL 7402,SMMC 7721, gene expression and tumor inhibition were studied in vitro and in BALB/c mouse model.ResultsAdeno associated virus mediated p53, p16 or p21 encoding gene could express in BEL 7402 cell line. Each individual type of recombinant AAV effected a significant induction of tumor cell apoptosis both in vitro and in vivo, the rate of apoptotic cells in vitro is about 30% and that of tumor growth inhibition is about 30～44%. And the apoptosis inducing efficiency was the highest after the tumor cell line was transfected by three recombinant AAV simultaneously, with a rate of 56% (in vitro) and 65% (in vivo).ConclusionNot only could all of the exogenous wild type p53, p16 and p21 genes mediated by AAV inhibit the growth of liver cancer cell lines, but also can the efficiency be significantly elevated by combined gene transfection.

关 键 词：重组腺相关病毒 抑癌基因 肝癌细胞系 凋亡 生长抑制 联合基因治疗 

分 类 号：R735.7[医药卫生—肿瘤] R730.51[医药卫生—临床医学]