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目的:研究瘤体内注射脂质体包裹的G-CSF基因的抗肿瘤作用及其可能机制。方法:将脂质体包裹的G-CSF基因直接注射至小鼠结肠癌瘤体内,观察G-CSF基因治疗的抗肿瘤效果及肿瘤细胞性状的变化。结果:瘤体内注射脂质体包裹的G-CSF基因后,可明显抑制结肠癌小鼠肿瘤的生长,显著延长存活期;配合大剂量化疗后效果更显著,有30%的小鼠存活90d以上。从瘤体内分离的肿瘤细胞,经G418(600μg/ml)抗性筛选后,产生抗G418的抗性克隆,并分泌人G-CSF(hG-CSF);经Northern-blot鉴定显示,该肿瘤细胞可表达G-CSFmRNA;肿瘤细胞表面表达ICAM-1分子、MHCⅠ类抗原(H-2Kd)均明显高于对照组。结论:瘤体内注射脂质体包裹的G-CSF基因后,可在肿瘤原位将G-CSF基因转染肿瘤细胞并有效表达,提高肿瘤细胞的免疫原性,有利于激活局部抗肿瘤免疫反应而发挥抗肿瘤作用
Objective: To study the anti-tumor effect of intratumoral injection of liposome-encapsulated G-CSF gene and its possible mechanism. METHODS: The liposome-encapsulated G-CSF gene was directly injected into mouse colon carcinoma, and the anti-tumor effect of G-CSF gene therapy and the changes of tumor cell traits were observed. RESULTS: After intratumoral injection of liposome-encapsulated G-CSF gene, the tumor growth of mice with colon cancer was significantly inhibited and the survival time was significantly prolonged. The effect was more significant with high-dose chemotherapy, and 30% of mice survived for more than 90 days. . Tumor cells isolated from the tumor cells were screened with G418 (600 μg/ml) resistance to produce resistant clones resistant to G418 and human G-CSF (hG-CSF) was secreted; this tumor cell was identified by Northern-blot identification. G-CSF mRNA can be expressed; the expression of ICAM-1 and MHC class I antigens (H-2Kd) on the surface of tumor cells was significantly higher than that of the control group. Conclusion: After intratumoral injection of liposome-encapsulated G-CSF gene, the G-CSF gene can be transfected into tumor cells in situ and effectively expressed in tumors, which can increase the immunogenicity of tumor cells and help activate local anti-tumor immune responses. And play an anti-tumor effect