白细胞介素-12与粒细胞巨噬细胞集落刺激因子联合基因治疗对小鼠肝癌的作用研究

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

作者信息

Qiu Shuangjian, Ye Shenglong, Wang Zhong, Tang Zhaoyiu, Lu Lina, Xiao Xiao

机构信息

Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2002 Dec;10(6):413-6.

PMID:12502439

Abstract

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 10(6) 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 microg and pXX-IL-12 12.5 microg; (2)pXX-IL-12 25 microg; (3)pXX-GM-CSF 25 microg; (4)pXX-Neo 25 microg. 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-gamma 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-gamma 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.

摘要

目的

研究白细胞介素-12（IL-12）与粒细胞-巨噬细胞集落刺激因子（GM-CSF）基因联合治疗对小鼠肝细胞癌的抗肿瘤作用。

方法

将24只皮下接种1×10⁶个BNL肝癌细胞的小鼠随机分为四组，每组6只，分别给予不同的细胞因子编码质粒：（1）pXX-GM-CSF 12.5μg和pXX-IL-12 12.5μg；（2）pXX-IL-12 25μg；（3）pXX-GM-CSF 25μg；（4）pXX-Neo 25μg。在肿瘤接种后第3天和第6天，采用基于流体动力学的通用DNA递送方法经尾静脉给予质粒。密切观察肿瘤生长和细胞免疫反应。同时观察质粒注射后血清中IL-12、GM-CSF和IFN-γ浓度的变化。