白细胞介素12基因治疗结肠癌的实验研究

目的观察携白细胞介素12(mIL-12)基因逆转录病毒载体的包装细胞(PA317-mIL-12)瘤内注射后,对肿瘤生长的抑制及对荷瘤动物生存的影响。方法在非免疫缺陷的结肠癌动物模型上分别施以化疗、放射免疫(放免)导向治疗、PA317-mIL-12基因治疗以及放免导向与IL-12基因联合治疗,比较各治疗组的肿瘤抑制效果和荷瘤动物的生存情况。结果经筛选后的携有mIL-12逆转录病毒载体包装细胞系PA317-mIL-12的上清,mIL-12浓度48h达27ng/106细胞。治疗3周后,IL-12基因治疗组(GT组)和IL-12基因与RIT联合治疗组(GT加RIT组)无论瘤体积还是瘤重量均明显低于对照组,生存率明显高于对照组(P<0.01)。结论PA317-mIL-12瘤内注射可有效抑制肿瘤生长,延长荷瘤动物的生存时间。基因治疗疗效优于化疗、放免导向治疗。放免导向与IL-12基因联合治疗疗效更佳。

Experimental study of interleukin 12 gene therapy on colon cancer

Objective To investigate the effects of interleukin 12 gene transfer on tumor growth, survival rate of tumor bearing mice. Methods Tumor bearing murine models were established with colonic cancer cells and PA317 mIL 12 carrying mIL 12 was constructed. Chemotherapy, radioimmunological treatment(RIT),gene treatment(GT) and combined RIT and GT were given in each group.Tumor volume and weight were measured, and survival rates were analyzed to compare their anti tumor effects. Results The packaging cell system(PA317 mIL 12) carrying pGCXEXPN mIL 12 expressed mIL 12. The concentration of mIL 12 in the supernatants reached 27 ng/106 cells after 48 hours.After treating with different schemes for 3 weeks, the tumor volume and tumor weight were significantly lower, and the survival rates of tumor bearing mice were significantly higher in GT group and combined GT and RIT group than those in chemotherapy and RIT groups. Conclusions Direct intra tumor injection of PA317 mIL 12 can effectively inhibit the growth of colon cancer. IL 12 gene transfer can also prolong the survival time of tumor bearing mice.