转基因表达的γ干扰素对小鼠结肠移植癌的细胞周期与细胞凋亡的影响

Therapeutic effects of IFN-γ gene transfection on cell cycle and apoptosis of tumor cells in colon tumor-bearing mice

目的研究γ干扰素(IFN-γ)转基因方法对荷瘤小鼠的细胞周期及细胞凋亡的影响。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A组(转基因治疗组)、B组(重组IFN-γ持续给药组)、C组(重组IFN-γ间断给药组)、D组(生理盐水组)及E组(空载质粒组)。采用流式细胞技术检测细胞周期与细胞凋亡。结果与D和E组比较,A组和B组的G0/G1期细胞的百分率及肿瘤细胞凋亡率明显增高(P<0.05)。结论IFN-γ转基因治疗可通过改变荷瘤小鼠的肿瘤细胞周期及促进凋亡来提高其抗肿瘤效果。

Objective To evaluate the effects of IFN-γ gene transfection on cell cycle and apoptosis of tumor cells in colon tumor-bearing mice. Methods Balb/c mice were used as animal model of subcutaneous inoculation of colon cancer cell CT26 . The tumor-bearing mice were divided into five groups with nine mice each, and treated with different methods. Animals in group A were treated with liposome-mediated gene transfection by eukaryotic expression plasmid of pcDNA3-IFN-γ, in group B intratumoral injection of recombinant IFN-γ daily for 4 weeks, in group C rIFN-γ injection 3 times per week for 4 weeks. The animals in group D were treated with daily saline injections as the control for group B and C. The mice in group E were injected with parent pcDNA3 plasmid as the control for group A, the empty plasmid injection was repeated after one week. The cell cycle and apoptosis were detected by flow cytometry. Results The tumor cell apoptosis and ratio of G0/C1 cell cycle cells in group A, B were higher than those in the control groups （P〈0. 05）. Conclusion IFN-γ transgenic therapy improves the therapeutic efficacy through interfering with cell cycle progression and promoting the apoptosis of tumor cells in tumor-bearing mice.