特异性增殖型腺病毒CNHK300-mIFN-γ治疗胃癌的体外实验研究

Antitumor effect on gastric cancer in vitro of selective replicative-competent adenovirus CNHK300-mIFN-γ

目的研究增殖型腺病毒CNHK300-mIFN-γ在胃癌细胞BGC．823中的特异性增殖能力、目的基因表达能力、肿瘤杀伤作用及安全性。方法通过增殖实验比较CNHK300-mIFN-γ与CNHK300在胃癌细胞BGC-823与成纤维细胞BJ中的增殖能力；ELISA法检测CNHK300-mIFN-γ和复制缺陷型腺病毒Ad-mIFN-γ不同细胞中mIFN-γ蛋白的表达量；MTT与细胞病变效应（CPE）实验观察CNHK300-mIFN-γ对胃癌细胞的杀伤效应及安全性。结果增殖实验结果表明CNI-IK300-mIFN-γ能选择性地在端粒酶阳性的胃癌细胞中大量增殖；ELISA实验结果表明CNHK300-mIFN-γ在胃癌细胞BCG-823中mIFN-γ的表达量可至（171．93±33．61）ng／ml，表达量高于复制缺陷型腺病毒Ad-mIFN-γ【（0．92±0．24）ng／ml]；MTT与CPE实验表明CNHK300-mIFN-γ对胃癌细胞BGC．823有较强的杀伤作用，对正常细胞并无明显杀伤。结论增殖型腺病毒CNHK300-mIFN-γ感染胃癌细胞BGC-823后能高效增殖并大量表达mIFN-γ蛋白，对胃癌细胞有明显杀伤作用且安全性良好。

Objective To compare the expression of mIFN-γ eplicative activities and anti-tumor activities of CNHK300mIFN-γand Ad-mIFN-γ in normal and gastric cancer cells. Methods The replicative activities of viruses in cells were measured by viral replication assay. CPE assay was used to detect the antitumor effect of viruses. The expression level of mIFN-γ in cancer cells was detected by ELISA. Results The infection of CNHK3OO-mIFN-~/led to an obvious expression of mIFN-γ n gastric cancer cells. The vector system CNHK300-mIFN-γ ossessed more replicated potential than Ad-mIFN-% and could specifically kill most of BGC-823 cells at MOI value of 0.1, which was much better than that by the traditional adenoviral vector. Conclusion CNHK300-mIFN-γ can selectively replicate and effectively express mIFN-γ in tumor cells, and specifically kill gastric cancer cells, suggesting a splendid future as a new anticancer agent.