多聚乙烯亚胺介导IL-12基因增强裸鼠抗骨肉瘤免疫

Polyethylenimine as a nonviral vector for interleukin-12 gene therapy to enhance the anti-osteosarcoma immunity in nude mouse

目的 :观察以多聚乙烯亚胺 (polyethylenimine ,PEI)为载体 ,体内转染小鼠白细胞介素 12 (inter leukin 12 ,mIL 12 )基因 ,治疗裸鼠骨肉瘤模型的疗效。方法 :以PEI为载体 ,体外转染mIL 12基因入人骨肉瘤细胞 ,并观察此基因表达情况。建立裸鼠骨肉瘤动物模型 ,将PEI包裹mIL 12基因直接注入肿瘤局部 ,检测此基因的蛋白表达情况和小鼠脾脏自然杀伤细胞 (NK)活性。结果 :在PEI/DNA治疗组小鼠的肿瘤局部 ,mIL 12蛋白水平明显升高 ,小鼠脾NK细胞活性增强。结论 :PEI可以成功的将mIL 12基因导入裸鼠骨肉瘤模型 ,mIL

Objective:To determine whether polyethylenimine(PEI),a polycationic DNA carrier,could be used to deliver the IL 12 gene into the nude mouse model of human osteosarcoma,and to observe the effect of gene therapy Method:Using PEI as the vector,murine interleukin 12(mIL 12)gene was delivered into human osteosarcoma cells,and observed its expression The nude mouse model of human osteosarcoma was established PEI IL12 plasmid complexes were introduced into the tumor by direct intratumor gene injection The gene expression was measured Lactic dehydrogenase(LDH)assay was used to evaluate the activity of natural killer(NK)cells Result:Incubation of MG63 cells in vitro with PEI IL12 plasmid complexes resulted in expression of both the p35 and p4O subunits of IL 12 mRNA and production of mIL 12 protein,we also demonstrated that treatment using PEI IL 12 plasmid complexes resulted in significant IL 12 expression in the tumor Greater activity of NK was also observed in the therapy group as compared with the controls Conclusion: PEI can successfully introduce mIL 12 gene into nude mouse model of human osteosarcoma,and IL 12 gene therapy is able to induce the host antitumor immune response efficiently