重组腺病毒介导γ-干扰素基因对小鼠结肠癌腹腔转移模型的实验治疗作用

Study of interferon-γ(IFN-γ) gene therapy on colon cancer and celiac metastases

背景与目的:肿瘤细胞靶向的细胞因子基因治疗是肿瘤治疗领域的研究热点。γ干扰素通过多种机制发挥抗肿瘤免疫的作用。本研究探讨利用γ-干扰素(IFN-γ)基因治疗对大肠癌的预防和治疗作用。方法:利用BALB/C小鼠成瘤的小鼠结肠癌CT26细胞株制备小鼠结肠癌腹腔转移瘤模型,用携带鼠IFN-γ基因的重组缺陷型腺病毒AdIFN-γ进行治疗,同时利用携带LacZ(β-galactosidase)基因的腺病毒AdLacZ和PBS(phosphate-bufferedsaline)作空白对照,检测经基因治疗后小鼠体内IFN-γ基因的表达情况、脾脏的细胞毒性T淋巴细胞(CTL)活性变化、肝转移的发生及荷瘤小鼠的生存期。结果:经IFN-γ基因治疗后,与对照组相比,治疗组小鼠血清中IFN-γ表达量明显增加(P<0.01),脾脏的CTL活性明显增强(P<0.05),肿瘤生长受到抑制,肝转移的发生率明显下降,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,并对其肝转移具有一定的预防作用。

Background and purpose： Gene therapy with taget cytokine of tumor cells is a hot research in the field of tumor therapy, IFN-γ, plays anti-tumor immune roles through multiple mechanisms. We investigated the anti-tumor effect and its mechanism of interferon-γ（IFN-γ） gene therapy on colon cancer. Methods： BALB/c mice were inoculated with CT26 cells （ murine colon carcinoma cell line） through intra-abdominal cavity to prepare an in vivo tumor model. Eight days after tumor inoculation, the tumor-bearing mice were divided into 3 groups and treated with one of the following preparations by intra-abdominal injection： AdIFN-γ, AdLacZ, and PBS, respectively. AdIFN-γ was characterized as replication-defective recombinant adenovirus encoding murine IFN-γ gene, AdlacZ encoding β- galactosidase. The expression of IFN-γ and the immunity function of mice were tested, and the tumor volume of mice was measured after gene therapy. The survival and the incident of liver metastasis were also analysed. Results： The level of IFN-γ in the serum and the CTL activity were increased significantly after gene therapy in the group treated with AdIFN-γ P 〈 0.01）. A profound and statistically significant improvement in terms of survival time for tumor-beating mice can be observed and the incidence of liver metastasis could be reduced when comparing with other groups of mice. Conclusions： Gene therapy with AdIFN-γ show promising results through inhibiting the tumor growth of colon cancer and reducing the possibility of liver metastasis.