G-CSF基因治疗及配合大剂量化疗对结肠癌小鼠的治疗作用

Antitumor Effects of G-CSF Gene Therapy on Colon Adenocarcinoma-Bearing Mice Receiving High-Dose Chemotherapy

粒细胞集落刺激因子(G-CSF)具有明显的促进粒系造血祖细胞分化成熟、有效地提高外周血白细胞数量的作用;体内单独应用还具有抑制肿瘤的生长、抗肿瘤转移的作用。为了探讨G-CSF基因治疗及其配合大剂量化疗后的体内抗肿瘤效果,我们以C-26结肠癌小鼠为模型,研究腹腔内移植成纤维细胞介导的G-CSF基因治疗,rhG-CSF直接注射治疗,以及分别配合化疗后对肿瘤的治疗作用。结果发现,rhG-CSF直接注射疗法可明显抑制早期结肠癌小鼠肿瘤的生长(P<0.01),明显延长早期荷瘤小鼠的存活期;G-CSF基因治疗可明显抑制早期、中期结肠癌小鼠肿瘤生长(P<0.01),明显延长早期、中期结肠癌小鼠的存活期(P<0.01)。配合大剂量化疗后,rhG-CSF注射疗法及G-CSF基因疗法可更明显地抑制结肠癌小鼠肿瘤的生长,更明显延长结肠癌小鼠的存活期。结果表明,G-CSF基因疗法可有效地延长结肠癌小鼠的存活期,配合大剂量化疗能更有效地发挥抗肿瘤作用,提高结肠癌小鼠的存活期;同时表明,G-CSF基因治疗具有比应用rhG-CSF更显著的体内抑制肿瘤的效果。

Granulocyte colony - stimulating factor (G - CSF) is a hematopoietic growth factor that is responsible for the differentiation and proliferation of hematopoietic progenitor cells to mature granulocyte, and can increase the number of peripheral neutrophils. It has been demonstrated that it could inhibit the metastasis of the murine tumors in spontaneous and experimental metastasis models by in vivo administration of recombinant human G - CSF. In order to examine the antitumor effect of G - CSF gene therapy on mice receiving high - dose chemotherapy, C - 26 colon adenocarcinoma - bearing mice which were prepared by S. c. injection of 1×105C-26 cells were i. p. injected with rhG-CSF (2μg/day×14day) or implanted with 1×107 collagen encapsulated NIH3T3-G-CSF cells which secrete high level of G - CSF after gene transfection. In our experiment, rhG-CSF could inhibit the tumor growth and extend the survival time of early stage C-26 bearing mice. However, G - CSF gene therapy could inhibit the tumor growth and prolong the survival both in early or middle stage C-26 mice. The results showed that both rhG - CSF and G - CSF gene therapy have exact antitumor effect and G - CSF gene therapy show more effective than rhG - CSF in vivo. Then we investigated the therapeutic effects of G - CSF gene therapy on C-26-bearing mice receiving high - dose chemotherapy (5-Fu 150mg/mice i. p.) . More effective results could be observed in C-26 - bearing mice receiving high dose chemotherapy after G - CSF gene therapy. The results also suggested that G-CSF gene therapy can inhibit the tumor growth more effectively both in C-26-bearing mice or C-26-bearing mice receiving high - dose chemotherapy.