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目的 用逆转录病毒载体 pLxSN转导TK基因 ,用真核表达载体 pIRES转导细胞因子基因 ,观察TK基因联合白介素 2 (mouseIL 2 ) /粒、巨噬细胞集落刺激因子 (mouseGM CSF)两种细胞因子基因对小鼠胃癌的治疗作用。方法 先用TK基因治疗胃癌细胞株 ,然后联合mIL 2 /mGM CSF基因治疗小鼠模型胃癌 ,其“自杀基因”与细胞因子基因相互协同 ,产生显著的抗肿瘤作用。RT PCR检测基因表达。结果 2 0 %的转基因细胞即可杀灭 70 %～ 80 %以上的肿瘤细胞 ,表现出很强的旁观者效应。实验表明 ,应用TK/ 9 丙氧鸟苷 (GCV ) ,即可产生很强的抗肿瘤作用 (P <0 .0 1)。结合mIL 2/mGM CSF两种细胞因子基因 ,抗肿瘤作用会得到进一步强化 ,肿瘤消退速度明显加快 ,大部分肿瘤完全消退。RT PCR显示 ,TK基因和mIL 2 /mGM CSF基因均能在组织中表达。结论 TK/GCV能够杀灭肿瘤细胞 ,具有显著抗肿瘤作用。联合IL 2 /GM CSF后 ,抗肿瘤作用会得到进一步强化 ,产生明显的抗肿瘤效应。
Objective To transduce TK gene with retroviral vector pLxSN and transduce cytokine gene with eukaryotic expression vector pIRES to observe the combination of TK gene with mouse IL 2/granulocyte macrophage colony stimulating factor (mouse GM CSF) Effect of factor gene on gastric cancer in mice. Methods TK gene was used to treat gastric cancer cell lines first, then mIL 2 /mGM CSF gene was used to treat mouse model of gastric cancer. Its “suicide gene” and cytokine genes were synergistic and produced significant anti-tumor effects. RT PCR detects gene expression. Results 20% of the transgenic cells could kill 70% to 80% of the tumor cells, showing a strong bystander effect. Experiments have shown that using TK/9 ganosine (GCV) can produce a strong anti-tumor effect (P < 0.01). Combining the two cytokine genes of mIL 2/mGM CSF, the anti-tumor effect will be further strengthened, the speed of tumor regression will be accelerated, and most of the tumors will completely disappear. RT PCR showed that both TK gene and mIL 2 /mGM CSF gene could be expressed in tissues. Conclusion TK/GCV can kill tumor cells and has a significant anti-tumor effect. Combined with IL 2 /GM CSF, the anti-tumor effect will be further enhanced, resulting in a significant anti-tumor effect.