mda-7／IL-24联合阿霉素诱导裸鼠肝癌凋亡的初步研究  

A preliminary study on apoptosis of hepatoma of nude mice treated by adenovirus-mediated mda-7/IL-24 combined with adriamycin

作　　者：夏岚[1] 薛新波[1] 陈堃[1] 王从俊[1] 李雁[2] 于愿[1] 吉文伟[1] 郑建伟[1] 胡回忆[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院胆胰外科中心,湖北武汉430030 [2]武汉大学中南医院肿瘤科、武汉大学肿瘤防治研究中心,湖北武汉430000

出　　处：《中国普通外科杂志》2008年第7期668-672,共5页China Journal of General Surgery

基　　金：湖北省科技攻关资助项目(2006AA304B52-4)

摘　　要：目的探讨重组腺病毒介导的mda-7/IL-24基因联合阿霉素(ADM)治疗裸鼠肝癌的作用及机制。方法采用mda-7/IL-24的重组腺病毒载体(Ad-mda-7)和/或ADM治疗实验性肝癌裸鼠,观察各组裸鼠生长时间及肿瘤体积变化,并对各组瘤体组织进行TUNEL检测。结果成功构建了重组腺病毒mda-7/IL-24基因载体。Ad-mda-7+ADM联合治疗组裸鼠平均生存时间为(83.8±4.82)d,明显长于其他3组(P<0.01);Ad-mda-7+ADM组肝癌体积明显缩小,抑癌率为79.78%,与单独用药组和对照组比较差异有统计学意义(P<0.05);联合组癌组织凋亡增加,凋亡指数为38.1%±4.2%,与其余3组比较差异有统计学意义(P<0.05)。结论重组腺病毒介导mda-7/IL-24联合阿霉素有明显的协同抗肿瘤作用,效果优于单独治疗组,主要作用机制与促进癌组织凋亡有关。Objective To study the effect and mechanism of adenovirus-mediated mda-7/IL-24 and/or adriamycin treatment of hepatoma in nude mice. Methods The recombinant adenovirus vector carrying melanoma differentiation-associated gene-7 （Ad-mda-7） and/or ADM were injected into the tumor-bearing mice. Their effects on the volume of the tumor and the survival rate of the mice were observed, and the apoptosis of cancer tissue was detected by TUNEL staining in each group. Results Ad-mda-7 was successfully constructed and expressed in vivo. Compared with the other three groups, the mice treated with Ad-mda-7 combined with adriamycin had longer average survival time （ 83.8 ± 4.82 ） d （ P 〈 0.01 ） ; the average Size of tumor in combined group was reduced significantly, the tumor inhibition rate was 79.78% , which was higher than the other groups （ P 〈 0. 05 ）. Enhanced induction of apoptosis by Ad-mda-7 combined with adriamycin was observed. The TUNEL-positive cells showed that apoptotic index in combination therapy group was 38. 1% ± 4. 2 % ,which was higher than that of the other 3 groups （P 〈 0. 05）.Conclusions Ad-mda-7 combined with adriamycin has stronger antitumor potency and has more synergistic effect on metastastic hepatoma mouse model than mda-7/IL-24 or adriamycin alone, and the mechanism is related to the promotion of apoptosis of tumor ceils.

关 键 词：癌 肝细胞 MDA-7/IL-24 阿霉素 基因治疗 细胞凋亡 

分 类 号：R735.7[医药卫生—肿瘤]