G-CSP基因治疗对大剂量化疗后结肠癌小鼠中性粒细胞数量和功能的影响

Effects of G-CSF Gene Therapy bn the Number and Functions of Peripheral Neutrophils of Colon Adenocarcinoma-Bearing Mice Receiving High-Dose Chemotherapy

中性粒细胞作为一种重要效应细胞在机体抗肿瘤过程中发挥重要的作用。为了探讨G-CSF基因治疗及大剂量化疗后对荷瘤小鼠中性粒细胞的影响以及G-CSF基因治疗后中性粒细胞在抗肿瘤中所起的作用,我们对G-CSF基因治疗后荷瘤小鼠中性粒细胞的数量和功能进行了研究。结果发现,G-CSF基因治疗与重组G-CSF(rhG-CSF)注射疗法相比,能更明显地提高结肠癌小鼠中性粒细胞的数量、中性粒细胞的吞噬功能、杀伤C-26细胞的活性以及分泌IL-1、TNF、NO水平。对大剂量化疗后的结肠癌小鼠,仍能明显提高中性粒细胞数量、吞噬功能、杀伤C-26结肠癌细胞的活性以及分泌IL-1、TNF、NO水平。表明G-CSF基因治疗比rhG-CSF注射疗法更有效地纠正并提高由于大剂量化疗后引起的外周血中性粒细胞的降低,增强中性粒细胞的杀伤活性,促进中性粒细胞分泌IL-1等细胞因子,发挥直接或间接的抗肿瘤作用。

Neutrophils play important role in anti - tumor response of tumor-bearing host as a kind of important effector cells. In order to identify the anti-tumor mechanisms of G-CSF gene therapy, we investigated the number and functions of the peripheral neutrophils in the C-26 colon adenocarcinoma-bearing mice receiving G - CSF gene therapy and high - dose chemotherapy. After G - CSF gene therapy, the number of neutrophils in peripheral blood was increased markedly in C-26 mice receiving high - dose 5 - Fu as compared with control groups including in vivo administration of rhG - CSF. The more potent cytotoxicity to C - 26 cells could be detected. The phagocytic activity, the secretion of IL-1, TNF, NO of the neutrophils were significantly enhanced. These data showed that G - CSF gene therapy can increase the number of neutrophils, activate the functions more effectively than in vivo administration of rhG - CSF.