表皮生长因子受体反义cDNA对大鼠C6脑胶质瘤的体内治疗作用

Department of Neurosurgery, Tianjing Medical University General Hospital.

Zhonghua Zhong Liu Za Zhi. 1998 Nov;20(6):422-4.

OBJECTIVE

To study the therapeutic effect of EGFR antisense cDNA on rat C6 glioma in vivo and find out the feasibility of using EGFR gene as a target in gene therapy of gliomas.

METHOD

Wild type C6 cells and C6 cells transfected with EGFR antisense cDNA were implanted stereotaxically to the caudate nucleus of right cerebrum of Wistar rats (control and transfected group, 8 and 6 rats respectively), and rats with cerebral tumor foci were treated with EGFR antisense cDNA mediated by Lipofectamine (treated group, 9 rats). The general manifestation, survival time, MRI features, histopathological change, proliferation activity and apoptosis of the gliomas in each group of rats were observed.

RESULTS

The mean survival time of control animals was 17.3 days. That of the 6 transfected and 6 treated animals was significantly prolonged. Four transfected and 3 treated rats were killed on day 28-90 after implantation for histopathological examination. The surviving time of the 4 remaining rats (1 transfected and 3 treated rats) was over 200 days. MRI demonstrated a distinct cerebral tumor in control rats, but the tumor foci were not found in the transfected rats and disappeared almost completely in the treated rats. The cerebral gliomas of rats after treatment with EGFR antisense cDNA showed decrease in proliferation activity and apoptosis.

CONCLUSION

The results of EGFR antisense cDNA in treatment of rat C6 glioma is encouraging. EGFR gene can be used as the target of gene therapy for malignant gliomas.

目的

研究表皮生长因子受体（EGFR）反义 cDNA 对大鼠 C6 胶质瘤的体内治疗效果，探讨以 EGFR 基因作为胶质瘤基因治疗靶点的可行性。

方法

将野生型 C6 细胞和转染了 EGFR 反义 cDNA 的 C6 细胞立体定向植入 Wistar 大鼠右大脑尾状核（对照组和转染组分别为 8 只和 6 只大鼠），对有脑肿瘤灶的大鼠用脂质体介导的 EGFR 反义 cDNA 进行治疗（治疗组 9 只大鼠）。观察各组大鼠胶质瘤的一般表现、生存时间、磁共振成像（MRI）特征、组织病理学变化、增殖活性及凋亡情况。

结果

对照组动物的平均生存时间为 17.3 天。转染组的 6 只和治疗组的 6 只动物生存时间显著延长。分别于植入后第 28 - 90 天处死 4 只转染大鼠和 3 只治疗大鼠进行组织病理学检查。其余 4 只大鼠（1 只转染大鼠和 3 只治疗大鼠）存活时间超过 200 天。MRI 显示对照组大鼠有明显脑肿瘤，而转染组大鼠未发现肿瘤灶，治疗组大鼠肿瘤灶几乎完全消失。用 EGFR 反义 cDNA 治疗后的大鼠脑胶质瘤增殖活性降低，出现凋亡。