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目的：探讨Ｇ－ＣＳＦ基因治疗配合大剂量化疗后的体内抗结肠癌肝转移的效果及其可能的机制。方法：制备Ｃ－２６结肠癌肝转移小鼠模型，观察成纤维细胞介导的腹腔途径Ｇ－ＣＳＦ基因治疗及其配合大剂量５－Ｆｕ后抗结肠癌肝转移的效果。结果：腹腔单独注射大剂量５－Ｆｕ或ｒｈＧ－ＣＳＦ后可明显地抑制Ｃ－２６肝转移结节形成（Ｐ＜０．０５），而腹腔内成纤维细胞介导的Ｇ－ＣＳＦ基因疗法的抗Ｃ－２６肝转移的作用更明显（Ｐ＜０．０１）；配合大剂量５－Ｆｕ后，Ｇ－ＣＳＦ基因疗法抗Ｃ－２６肝转移的效果比单独应用ｒｈＧ－ＣＳＦ或Ｇ－ＣＳＦ基因治疗更明显，且优于ｒｈＧ－ＣＳＦ注射疗法与大剂量５－Ｆｕ联合的治疗效果。经Ｇ－ＣＳＦ基因治疗后小鼠腹腔巨噬细胞吞噬功能、抗原提呈能力、杀伤活性，以及分泌ＴＮＦ、ＮＯ、ＩＬ－１的能力均有明显提高。结论：Ｇ－ＣＳＦ基因治疗配合大剂量化疗可有效地抗结肠癌肝转移，腹腔巨噬细胞功能的增强可能是其机制之一。
Objective: To investigate the effect of G-CSF gene therapy combined with high-dose chemotherapy on liver metastasis in colon cancer and its possible mechanism. METHODS: A mouse model of C-26 colon cancer liver metastasis was prepared, and the effect of fibroblast-mediated G-CSF gene therapy in the abdominal cavity and anti-colon cancer liver metastasis after high-dose 5-Fu was observed. RESULTS: Intraperitoneal injection of large doses of 5-Fu or rhG-CSF significantly inhibited the formation of C-26 hepatic metastatic nodules (P<0.05), whereas intraperitoneal fibroblasts mediated G-CSF gene therapy The effect of anti-C-26 hepatic metastasis was more obvious (P<0.01); the effect of G-CSF gene therapy on liver metastasis of C-26 was higher than that of rhG-CSF or G-CSF alone when combined with large doses of 5-Fu. The treatment is more obvious and superior to the combined effect of rhG-CSF injection therapy and high-dose 5-Fu. The ability of peritoneal macrophages to undergo phagocytosis, antigen presentation, and killing activity as well as the ability to secrete TNF, NO, and IL-1 after G-CSF gene therapy were significantly improved. Conclusion: G-CSF gene therapy combined with high-dose chemotherapy can effectively prevent liver metastasis of colon cancer. Enhancement of peritoneal macrophage function may be one of the mechanisms.