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目的 观察自杀基因TK对小鼠胃癌的杀伤作用 ,并联合mGM CSF基因 ,观察免疫反应在增强TK杀伤性中的作用。方法 应用逆转录病毒方法转导自杀基因TK ,应用脂质体方法转导细胞因子基因mGM CSF。观察TK基因体外对小鼠胃癌 6 15小鼠前胃癌 (MFC)细胞的杀伤性和旁观者效应 ;体内实验中将病毒上清注入瘤体内 ,并结合应用其前药 9 丙氧鸟苷 (GCV)和mGM CSF基因 ,分别观察肿瘤的生长情况。通过病理切片观察肿瘤病理变化 ;应用酶联免疫吸附试验 (ELISA)方法测定 40只小鼠mGM CSF的产量。结果 2 0 %的转TK基因细胞可以杀伤 70 %～ 80 %以上的肿瘤细胞。体内实验表明TK基因结合GCV可显著杀伤肿瘤 ,而TK基因本身并无杀伤作用 (P <0 .0 5 )。联合mGM CSF后肿瘤体积显著缩小 ,4只小鼠肿瘤完全消退 ,与TK/GCV比较差异有非常显著性 (P <0 .0 1)。结论 TK基因联合GCV对小鼠胃癌产生显著杀伤作用 ,不仅转基因细胞被杀死 ,而且通过旁观者效应杀伤大量周围细胞。细胞因子基因mGM CSF可增强TK的抗肿瘤作用。
Objective To observe the killing effect of suicide gene TK on gastric cancer in mice and combine mGM CSF gene to observe the role of immune response in enhancing TK killing. Methods Transduction of the suicide gene TK by retrovirus method and transduction of the cytokine gene mGM CSF by liposome method. Observe the killing and bystander effect of TK gene on mouse gastric cancer 6 15 mouse MFC in vitro. Virus supernatant was injected into the tumor in vivo and combined with its prodrug 9 ganosine (GCV). ) and mGM CSF gene, respectively, to observe the growth of the tumor. The pathological changes of the tumor were observed by pathological section; the production of mGM CSF in 40 mice was determined by enzyme-linked immunosorbent assay (ELISA). Results 20% of TK-transfected cells killed 70% to 80% of tumor cells. In vivo experiments showed that TK gene combined with GCV can significantly kill tumors, while TK gene itself has no killing effect (P < 0.05). After the combination of mGM and CSF, the tumor volume was significantly reduced, and the tumors of 4 mice completely subsided, showing a significant difference from TK/GCV (P < 0.01). Conclusion The TK gene combined with GCV has a significant killing effect on gastric cancer in mice. Not only the transgenic cells were killed, but also a large number of peripheral cells were killed by the bystander effect. The cytokine gene mGM CSF enhances the antitumor effect of TK.