脂质体介导IFN-γ基因治疗荷大肠癌小鼠的实验研究

The anti-tumor effect of lipofectamine mediated interferon-γ gene therapy on experimental colon cancer model

目的探讨利用γ 干扰素 (interferon γ ,IFN γ)基因对大肠癌的治疗作用及其作用机制。方法构建携带IFN γ基因的真核表达质粒pcDNA3 IFN γ ,以脂质体作载体 ,对荷大肠癌小鼠行瘤体内注射IFN γ基因 ,检测经基因治疗后小鼠体内IFN γ基因的表达、脾脏的细胞毒性T淋巴细胞 (cyto toxicTlymphoctye,CTL)活性、肿瘤的大小、肿瘤局部的淋巴细胞浸润情况及荷瘤小鼠的生存期。结果经IFN γ基因治疗后 ,治疗组小鼠血清中IFN γ表达量和脾脏的CTL活性明显增强 (P <0 0 1) ,肿瘤局部淋巴细胞浸润明显 ,肿瘤生长受到抑制 ,荷瘤小鼠的存活期明显延长。结论利用IFN γ基因治疗大肠癌具有明显的疗效。

Objective To investigate the anti-tumor effect of interferon-γ(IFN-γ) gene therapy on colon cancer. Methods BALB/c mice were inoculated subcutaneously with CT26 (murine colon carcinoma cell line) cells to prepare an in vivo tumor model. Eight days after tumor inoculation,the tumor-bearing mice were divided into 3 groups and injected intra-tumorally with one of the following preparations: pcDNA3-IFN-γ/Lipofectamine,pcDNA3 /Lipofectamine,and PBS respectively. The expression of IFN-γ,the immunity function of mice,the histological changes of the tumor,the tumor volume in tumor-bearing mice were tested after gene therapy. ResultsThe level of IFN-γ in the serum and the CTL activity increased significantly( P <0.01) after gene therapy. The growth suppression of the established tumors and the protective lymphocytes accumulation was found in local tumor. Gene therapy significantly prolongs the survival of tumor-bearing mice. [WT5”HZ]ConclusionExperimental IFN-γ gene therapy improves the positive immune reaction of host mice against the inoculated colon cancer.