IL-12与粒细胞-巨噬细胞集落刺激因子基因联合治疗小鼠肝癌的研究

Study on the effects of combined IL-12 and GM-CSF gene therapy for murine liver cancer

目的 研究L-12与粒细胞-巨噬细胞集落刺激因子(granalocyte-macrophage-colong scimulatingfactor,GM-CSF)联合基因治疗对小鼠皮下肝癌的治疗作用。方法 将皮下接种1×106BNL肝癌细胞的小鼠分四组于肿瘤接种3、6d后分别经尾静脉高压注射总量为25μg的细胞因子编码质粒:(1)pXX-GM-CSF、pXX-IL-12各 12.5μg;以pXX-IL-12 25μg;(3)pXX-GM-CSF 25μg;(4)pXX-Neo 25μg,每组6只小鼠。观察小鼠皮下肿瘤生长情况及所诱导的细胞免疫反应。同时研究了经尾静脉高压注射后小鼠血清IL-12、GM-CSF和IFN-γ浓度变化。结累IL-12与GM-CSF联台基因治疗可以诱导更强的抗肝癌免疫和细胞免疫反应。GM-CSF可以增强IL-12分泌并减少其诱导的IFN-γ分泌。结论IL-12和GM-CSF联台基因治疗可以产生较强的抗瘤作用并能减少IL-12的副作用。

Objective To study the anti-tumor effects of combined IL-12 and granalocyte-macrophage-colong scimulating factor (GM-CSF) gene therapy on murine hepatocellular carcinoma. Methods Twenty-four mice received subcutaneous inoculation of 1 x 106 BNL hepatoma cells were randomly divided into the following four groups with different cytokine encoding plasmids (6 mice for each group): (1 )pXX-GM-CSF 12.5 Mg and pXX-IL-12 12.5 pg; (2)pXX-IL-12 25 u g; (3)pXX-GM-CSF 25 ng; (4)pXX-Neo 25 tig. The plasmids were given through tail vein using a versatile hydrodynamics-based DNA delivery method on day 3 and day 6 after tumor challenge. The growth of tumor and cellular immune response were observed intensively. The changes in serum concentration of IL-12, GM-CSF, and IFN-v after plasmids injection were also observed. Results Co-delivery of IL-12 and GM-CSF could mount stronger anti-tumor effects, longer term enhanced IL-12 expression and lower level of IFN-v than did IL-12 alone. Conclusions Combined IL-12 and GM-CSF can render a strong anti-tumor effect as well as a potential to lower the side effects.