反义IGF-IR基因片段对裸鼠胶质瘤形成的影响

目的 探讨胰岛素样生长因子-I受体(IGF—IR)的反义基因片段对裸鼠胶质瘤的形成及其病理的影响。方法 体外用反义IGF—IR基因片段孵育胶质瘤细胞，并接种裸鼠体内，了解其肿瘤形成能力及其肿瘤组织学和IGF—IR的表达：结果 野生型C6细胞和正义寡核苷酸孵育的C6细胞在BALB／c裸鼠体内形成肿瘤的潜伏期均为4d，而经反义寡核苷酸孵育的C6细胞在裸鼠体内形成肿瘤的潜伏期为11～12d，肿瘤形成的潜伏期明显延长，肿瘤的生长得到抑制。肿瘤形成7d时，研究发现正义核酸组与野生组肿瘤病理组织学是一致的，且IGF—IR均呈高表达，反义核酸组肿瘤细胞变得稀疏，而且可见部分肿瘤细胞核固缩，染色质凝聚边缘化，甚至有细胞出现核碎裂等凋亡征象，IGF—IR表达明显减少。而在肿瘤形成的25d时，反义核酸组胶质瘤的病理表现和IGF—IR蛋白的表达与对照组和正义核酸组无明显差异。结论反义IGF—IR基因片段能抑制裸鼠胶质瘤的形成能力，但逃脱反义IGF—IR基因片段封闭的肿瘤细胞经过体内的增殖可形成肿瘤。

The effects of antisense phosphorothioate oligodeoxynucleotide to IGF-IR mRNA on the glioma formation in nude mice

Objective To investigate the effects of antisense phosphorothioate oligodeoxynucleotide to insulin-like growth factor I receptor (IGF-IR) mRNA on inhibition of glioma growth in nude mice.Methods The wild-type C6 cells preincubated with antisense oligodeoxynucleotides (ODNs) were injected subcutaneously into nude mice, the tumor formation, growth, its pathology and the expression of IGF-IR were studied. Results The wild-type C6 cells preincubated with antisense ODNs gave rise to tumor with latent period of 11 to 12 days when injected subcutaneously into nude mice, while the same wild-type C6 cells or the same cells preincubated with sense ODNs gave rise to tumors with the latent period of 4 days. On the seventh day after tumor formation in nude mice, pathological tissue of sense tumor was the same as wild-type tumor, whereas tumor cell in antisense animal was sparse and present of apoptotic changes. The expression level of IGF-IR was high in sense and wild-type tumor, when the expression level of IGF-IR in antisense tumor was lower. On 25th day after tumor formation in nude mice, the cell from antisense tumor was of the same morphology as sense and wild-type tumor. The expression level of IGF-IR in antisense tumor was consistent with sense and wild-type tumor.Conclusion Antisense ODNs can reduce tumorigenicity greatly in vivo. The delayed tumor growth of antisense cell could be due to that cells treated by antisense ODNs underwent apoptosis in large numbers by inhibition expression of IGF-IR, the few cells that survive could escape antisense ODNs action and then proliferate rapidly and form tumor.