论文部分内容阅读
目的 观察白介素18和胞嘧啶脱氨酶基因对小鼠肝癌MM45T.Li联合基因治疗的效果。 方法 将小鼠IL-18基因克隆入pGCEN中，构建成pGCEN/IL-18。包装成逆转录病毒，感染小鼠肝癌细胞MM45T.Li, 制出具有生物活性的MM45T.Li/IL-18瘤苗，灭活后对荷瘤小鼠进行皮下接种。同时利用AdCD/5FC对小鼠肝癌原位注射，进行联合基因治疗。 结果 在接受治疗30d后，MM45T.Li对照组肿瘤体积1580～1625mm3，MM45T.Li/IL-18治疗组（366±159）mm3，AdCD/5FC治疗组（438±65）mm3，IL-18和AdCD/5FC联合治疗组体积（15±7）mm3（P＜0.05）。MM45T.Li对照组中位生存期50.0～51.5d，MM45T.Li/IL-18治疗组65d，AdCD/5FC治疗组57d，联合治疗组76d，和单独治疗组相比，联合治疗组中位生存期明显延长（P＜0.05）。联合基因治疗组肿瘤组织周围有更多CD4+及CD8+淋巴细胞浸润。 结论 IL-18和CD基因的联合治疗组，其疗效要明显好于IL-18或CD基因单独治疗组。进行联合基因治疗，既有效地减少了肿瘤负荷，又充分调动了机体的抗肿瘤免疫，提高了疗效。
Objective To observe the effect of interleukin-18 and cytosine deaminase gene on gene therapy of mouse liver cancer MM45T.Li. Methods The mouse IL-18 gene was cloned into pGCEN and constructed into pGCEN/IL-18. The retrovirus was packaged and the mouse hepatoma cell line MM45T.Li was infected to produce a biologically active MM45T.Li/IL-18 tumor vaccine. After inactivation, the tumor-bearing mice were inoculated subcutaneously. At the same time, using AdCD/5FC to inject the mouse liver cancer in situ and perform combined gene therapy. Results After 30 days of treatment, the tumor volume of MM45T.Li control group was 1580～1625mm3, MM45T.Li/IL-18 treatment group was (366±159)mm3, AdCD/5FC treatment group was (438±65)mm3, IL-18 and The volume of AdCD/5FC combined treatment group was (15±7) mm3 (P<0.05). The median survival time of the MM45T.Li control group was 50.0 to 51.5 days, 65 days for the MM45T.Li/IL-18 treatment group, 57 days for the AdCD/5FC treatment group, 76 days for the combined treatment group, and the median survival for the combined treatment group compared with the treatment alone group. The period was significantly longer (P<0.05). In the combined gene therapy group, more CD4+ and CD8+ lymphocytes infiltrated around the tumor tissue. Conclusion The combined treatment of IL-18 and CD gene has a better therapeutic effect than the IL-18 or CD gene alone treatment group. The combined gene therapy can effectively reduce the tumor burden, fully mobilize the body’s anti-tumor immunity, and improve the efficacy.