反义IGF-1抑制脑胶质瘤体内外增殖的实验研究

Experimental Study of Inhibitory Effect of Antisense IGF-I on Glioma Proliferation in Vivo & in Vitro

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C_6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-C_6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C_6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C_6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。

Objective: To study the exact role of IGF-I in the development of glioma and the effective target for gene therapy against 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(Wistar rat) bearing subcutaneous C6 tumor was set up, through which the different biologic characters 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 large continuously. Around the tumors,apoptotic cells and mononuclear lymphocytes increased and the IGF-I expression and cell proliferative potential decreased in the therapeutic group. Conclusion:The antisense IGF-I mRNA strategy might be a sound therapeutic modality against neoplasms. Its mechanism based not only on the antisense-mediate inhibition of IGF-I expression but also on the antisense-mediate enhancement of immune response of the host.