【摘要】 目的:评价IFN-γ转基因方法与肿瘤内注射重组IFN-γ对荷瘤小鼠的治疗作用。方法:用小鼠结肠癌细胞CT26接种于Balb/c小鼠皮下,建立小鼠皮下种植模型;小鼠成瘤后分成5组(每组9只),分别进行不同的干预。A组,瘤内注射阳离子脂质体Lipofectamine和含huIFN-γ全长基因的真核表达质粒pcDNA3-huIFN-γ的混合液,1周后重复1次;B组,瘤内注射重组huIFN-γ,每日1次,连续4周;C组,瘤内注射重组huIFN-γ,每周3次,连续4周;D组,瘤内注射生理盐水,每日1次,连续4周;E组,瘤内注射空载质粒pcDNA3与Lipofectamine的混合液,1周后重复1次。比较种植瘤的体积,并取肿瘤组织进行病理学检查及FCM分析。结果:与D、E组比较,A、B、C组抑瘤效应明显;A、B、C组皮下肿块镜下观察见大量淋巴细胞浸润,流式细胞仪检测显示CD3+、CD4+T淋巴细胞的百分率明显高于D、E组。结论:IFN-γ转基因治疗对荷瘤小鼠的肿瘤生长有抑制效应,转基因治疗组与重组IFN-γ每日给药组抑瘤效果相当,而优于重组IFN-γ间断给药组。更多还原

【Abstract】 Objective: To evaluate the therapeutic effects of IFN-γ gene transfer compared to intratumoral injection of recombinant IFN-γ in tumor-bearing mice. Methods: Balb/c mice were used as the animal model and were inoculated subcutaneously with colon cancer cell line CT26. The tumor-bearing mice were divided into five groups (9 mice in each group) and were treated with different methods. A mixture of pcDNA3-huIFN-γ, a eukaryotic expression vector containing the full-length IFN-γ gene, and lipofectamine was injected intratumorally twice into the mice in Group A with a one-week interval. In Group B, the tumor-bearing mice received intratumoral injections of recombinant IFN-γ daily for 4 weeks. In Group C, the recombinant IFN-γ was administered three times per week for four weeks. In Group D, the mice were injected with saline daily for 4 weeks. Parent pcDNA3 vector injection was conducted in Group E to serve as the control. The empty vector injection was repeated after one week. The tumor volume was measured and the tumor tissues were removed and collected for pathological examination and flow cytometry analysis. Results: Tumor regression was conspicuous in Group A, B and C, compared to group D and E. Excess lymphocyte infiltration of the subcutaneous tumors can be seen microscopically in Group A, B and C and the percentage of CD3+ and CD4+ T-lymphocytes was significantly higher in those groups than that in Group D or E based on flow cytometry data. Conclusion: IFN-γ expressed by the vector had an inhibitory effect on tumor growth in tumor-bearing mice. The therapeutic effect of the group treated with the IFN-γ vector is identical to that of the group that received daily intratumoral rIFN-γ injections, but it is better than that of the group that received intermittent rIFN-γ injections.更多还原