反义IGF—1抑制脑胶质瘤体内外增殖的实验研究

目的：明确IGF－1在肿瘤发生发展中的作用，为基因治疗优选靶的。方法：（1）转染含反义IGF－1cDNA的表达型质粒至鼠C6胶质瘤细胞，对比转染前后细胞IGF－1的表达、增殖活性等变化。（2）对Wistar大鼠－C6胶质瘤动物模型实施反义IGF－1基因治疗，对比治疗与否肿瘤大小、IGF－1表达、淋巴细胞浸润等的差别。结果：（1）含反义质粒的C6细胞系IGF－1表达减低，增殖活性下降约35％。（2）反义IGF－1治疗后的肿瘤8周内完全消失，而对照组持续增大，治疗组肿瘤的凋亡细胞、淋巴细胞浸润增加，IGF－1表达、细胞增殖活性下降，结论：反义IGF－1基因转染能有效抑制C6胶质瘤的体内外增殖，增殖活性下降和免疫系统攻击可能是双重原因。

xperimental Study ofInhibitory Effect of Antisense IGF-I on Glioma Proliferation in Vivo & in Vitro

Objective: To study the exact role of IGF-I in the development of glioma and the effective target for gene therapyagainst brain tumor. Methods: (1)An antisense IGF-I mRNA strategy was performed in rat C6 glioblastoma cells with lipo-fectamine assay. The levels of IGF-I expression and cell proliferative potential before and after transfection were compared.(2) A rodent animal model (Wist ar rat ) beating subcutaneous C6 tumor was set up, through which the different biologiccharacters before and after the gene treatment of antisense IGF-I were analyzed. Results: Compared with their parental cells,the transfected C6 cells that expressed IGF-I on a relative low level cut down their proliferative potential about 35 %. (2)Within 8 weeks,the tumors treated with antisense IGF-I disappeared completely,while those in control group became largecontinuously. Around the tumors,apoptotic cells and mononuclear lymphocytes increased and the IGF-I expression and cellproliferative potential decreased in the therapeutic group. Conclusion:The antisense IGF-I mRNA strategy might be a soundtherapeutic modality against neoplasms. Its mechanism based not only on the antisense-mediate inhibition of IGF-I expres-sion but also on the antisense-mediate enhancement of immune response of the host.