反义IGF-1基因治疗C6鼠脑胶质瘤的体内实验研究

目的 明确IGF－1在脑肿瘤发生发展中的作用并为基因治疗优选靶的。方法 采用Wistar大鼠C6脑胶质瘤模型进行反义IGF－1基因治疗，通过MRI及病理活检等手段。动态观察，分析各时限治疗组与对照组动物（每组10只）肿瘤的判别，结果（1）颅内种植肿瘤后，反义治疗组肿瘤不断 减小至8周后几乎完全消失，动物生存期超过80天的观察期，对照组均因肿瘤增大在2周期前后死亡；（2）治疗组肿瘤相对于同时限对照组者凋亡细胞，淋巴细胞浸润增加，IGF－1表达，细胞增殖活性有所下降，结论反义IGF－1基因治疗能有效抑制大鼠体内胶质瘤的恶性进展，IGF－1表达减少使用细胞增殖活性下降和免疫系统攻击增强可能是治疗组肿瘤消失的双重原因。

Trearment of rat C6 glioblastoma by an antisense IGF-1 sirategy: an in vivo study

Objective This study was to discuss the exact role of IGF 1 in the development of glioma and to filtrate an effective target for the gene therapy of the brain tumors. Methods An antisense IGF 1 mRNA strategy was performed into the rat C6 glioblastom cells with the liporfecamine assay. A further study was followed by setting up a rodent animal model (Wistar rat) bearing C6 glioma, through which the different biologic characters between the gliomas with and without antisense IGF 1 mRNA were analyzed by pathological observation as well as MRI scanning, etc. Results (1) All the animals of control groups, bearing parental C6 glioma, were died of tumor around 2 weeks after tumor injection, while those of the therapeutic groups treated by antisense IGF 1mRNA, kept alive beyond 80 days with the completely disappearing of the tumor mass. (2) Compared with the control groups, it was found that a relative increase of apoptotic cells and mononuclear lymphocytes accompanied with a decrease of IGF 1 expression and cell proliferative potential around the tumor site of therapeutic groups.Conclusions The complete regression of glioma in this experiment indicates that antisense IGF 1 strategy, might be a sound therapeutic modality against brain tumors, however, the mechanism of this strategy based not only on the antisense mediated inhibition of IGF 1 expression but also on the antisense mediated enhancement of immune response of the lost.