增殖型腺病毒载体介导mIL-12基因对胃癌细胞的杀伤作用(英文)  

Treatment of gastric cancer with replication-competent adenovirus carrying inte rleukin-12 gene

作　　者：薛绪潮 方国恩[1] 张琪[2] 薛惠斌[2] 毕建威[1] 曹贵松[1] 钱其军[2] 

机构地区：[1]第二军医大学长海医院普通外科,上海200433 [2]第二军医大学东方肝胆外科医院病毒基因治疗实验室,上海200438

出　　处：《第二军医大学学报》2004年第1期75-79,共5页Academic Journal of Second Military Medical University

基　　金：This work is supported by the Major Interna-tional Cooperation Projectof National Natural Science Foundation ofChina ( 3 0 12 0 160 82 4) and the State High Technology R&D Projectof China( 2 0 0 1AA2 170 3 1)

摘　　要：目的 :观察增殖型腺病毒载体介导的 m IL - 1 2基因对胃癌细胞的杀伤作用。 方法 :利用携带 m IL - 1 2基因的增殖型腺病毒转染胃癌细胞株 SGC- 790 1 ,通过病毒增殖实验、细胞病理效应、酶链免疫反应等分别观察病毒复制能力、病毒对胃癌细胞的杀伤作用及 m IL - 1 2表达水平。结果 :携带 m IL - 1 2基因的增殖型腺病毒转染胃癌细胞株 SGC- 790 1具有肿瘤增殖型腺病毒 ONYX- 0 1 5的相似作用 ,可在肿瘤细胞内复制、增殖并杀死肿瘤细胞 ,而并不能在正常细胞内复制及增殖。该病毒在肿瘤细胞内的增殖能力是传统载体的近千倍。该载体携带的 m IL - 1 2基因的表达量明显高于传统基因治疗的腺病毒载体体系 ,是传统基因治疗表达量的百倍。 结论 :CNHK2 0 0 - m IL - 1 2能在胃癌细胞中增殖并杀死胃癌细胞 ,并提高目的基因的表达水平 。Objective: To investigate antitumor effects of a replication competent adenovirus carrying mouse interleukin 12 gene on gastric cancer. Methods: Replication competent adenovirus carr ying mouse IL 12 gene (CNHK200 mIL 12) was constructed to transfect gastric c arcinoma cell line SGC 7901. The cytopathic effect, the expression of the mouse IL 12 gene, and the replication of the virus were observed respectively by cell pathology, ELISA and virus replication assay. Results: The vector system, CNHK200 mIL 12, possessed the same characteristic a s the replicative adenovirus ONYX 015, replicating and proliferating in the gastric carcinoma cells but not in the normal cells, thus specifically killing gastric carcinoma cells. The replication level of CNHK200 mIL 12 in the gastric carcinoma cells was more than one thousand times higher compared with that of the conventional adenovirus vector; the mIL 12 expression level increased by 100 folds compared with that of the conventional adenovirus vector carrying mIL 12 gene. Conclusion: CNHK200 mIL 12 can replicate specifically in gastric carcinoma cells and kill them. Meanwhile, it greatly increases the target gene expression, suggesting that CNHK200 mIL 12 may be used to treat gastric carcinoma.

关 键 词：增殖型腺病毒载体 MIL-12 胃癌 癌细胞 杀伤作用 基因疗法 白细胞介素12 

分 类 号：R735.2[医药卫生—肿瘤] R730.54[医药卫生—临床医学]