巨噬细胞炎症蛋白-1α对小鼠肝癌的基因治疗  

Experimental gene therapy mediated by macrophage inflammatory protein-1α for murine liver cancer

作　　者：杨庆[1] 卫立辛[1] 贾凤岐[1] 杨广顺[1] 吴孟超[1] 郭亚军 

机构地区：[1]第二军医大学东方肝胆外科研究所肿瘤免疫与基因治疗中心,上海200438 [2]国际合作肿瘤研究所

出　　处：《中华消化杂志》2002年第9期519-522,共4页Chinese Journal of Digestion

基　　金：上海市卫生系统百名优秀学科带头人培养基金项目( 3119975 0 30 2 10 40 3)

摘　　要：目的　观察重组腺病毒载体介导的小鼠巨噬细胞炎症蛋白 1α(MIP 1α)对小鼠肝癌的基因治疗效果。方法　携带小鼠MIP 1α基因的腺病毒载体 (AdmMIP 1α)体外感染小鼠肝癌细胞株Hepa1 6 。 48h后 ,用载体自身报告基因表达的绿色荧光蛋白检测感染效率 ;RT PCR法检测感染后细胞内MIP 1α的表达 ;每天计数细胞 ,观察细胞的体外生长曲线。皮下接种Hepa1 6细胞建立小鼠肝癌模型 ,肿瘤局部分别单次注射 1× 10 9cfu的AdmMIP 1α、空载体对照 (Ad empty)和PBS ,观察肿瘤大小和小鼠生存期。结果　腺病毒载体AdmMIP 1α体外能有效地感染靶细胞Hepa1 6 ,并在感染后的细胞内检测到mMIP 1α的mRNA ,体外感染对Hepa1 6的生长曲线无显著影响。瘤体内单次注射AdmMIP 1α导致 4/ 9只小鼠肿瘤完全消退 ,并延长小鼠生存期 ,与对照组比较 ,差异有显著性 (P <0 .0 0 1)。结论　腺病毒介导的MIP 1α基因治疗对小鼠肝癌有一定的效果 。Objective To observe the in vivo therapeutic effects on murine liver cancer mediated by macrophage inflammatory protein-1α(MIP-1α) recombinant adenoviral vector. Methods The adenoviral vector bearing gene MIP-1α(AdmMIP-1α) was infected with hepatocarcinoma cell strain Hepa1-6. After forty-eight hours the infection efficacy was measured by green fluorescent protein expression and the mRNA of MIP-1α was detected by RT-PCR. The cell number was counted daily until the fourteenth day. Liver cancer model was established by subcutaneous inoculation of Hepa1-6 cells. A single dosage of 1×10 9 cfu AdmMIP-1α, Ad-empty or PBS was injected intratumorally. The tumor volume and survival rate were measured twice a week. Results Adenoviral vector could efficiently infect Hepa1-6 cells in vitro and lead to the transcription of high levels of mMIP-1α mRNA. The infection in vitro had no significant influence on the growth curve of Hepa1-6. Compared with untreated tumors or tumors injected with control vector, the tumor growth in vivo was significantly inhibited by one single intratumoral administration of AdmMIP-1α, leading to complete regression in 44% mice. This treatment also significantly increased survival rate. Conclusions MIP-1α gene transfer mediated by recombinant adenoviral vector has therapeutic effects on Hepa1-6 liver cancer, and thus might become a cancer gene therapy candidate for further clinic application.

关 键 词：巨噬细胞炎症蛋白-1Α 小鼠 肝癌 腺病毒介导 趋化因子 基因治疗 

分 类 号：R735.7[医药卫生—肿瘤]