增殖型腺病毒载体介导mIL-12基因对胃癌细胞的杀伤作用

目的:观察增殖型腺病毒载体介导的mIL-12基因对胃癌细胞的杀伤作用.方法:利用携带mIL-12基因的增殖型腺病毒转染胃癌细胞株SGC-7901,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mIL-12表达水平.结果:携带mIL-12基因的增殖型腺病毒转染胃癌细胞株SGC-7901具有肿瘤增殖型腺病毒ONYX-015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mIL-12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:CNHK200-mIL-12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,可能为胃癌治疗提供一新途径.

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

Objective: To investigate antitumor effects of a replication-competent adenovirus carrying mouse interleukin-12 gene on gastric cancer. Methods: Replication-competent adenovirus carrying mouse IL-12 gene (CNHK200-mIL-12) was constructed to transfect gastric carcinoma 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 as 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.