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目的 研究连接蛋白 (Cx) 4 3基因抑制脑胶质瘤生长的作用。方法 将Cx43基因表达缺失的大鼠C6胶质瘤细胞 (对照组 )和转染Cx43cDNA的C6细胞 (转染组 )种植于SD大鼠右侧尾状核 ,荷载C6脑胶质瘤鼠用Cx43cDNA原位治疗 (治疗组 ) ,并以空载体治疗作为对照 (空载组 ) ,每组 10只 ,观察各组大鼠一般情况、生存期、MRI动态变化及病理改变。通过原位杂交及免疫组化染色检测肿瘤Cx43mRNA及蛋白表达 ,以AgNOR平均计数检测增殖活性 ,以Tunel法检测细胞凋亡。结果 对照组和空载组大鼠均于 3周内死亡 ;转染组 6只大鼠和治疗组 8只大鼠观察 12 0d内无自然死亡。除治疗组 1只尚有残瘤外 ,余瘤体消失。转染组和治疗组肿瘤细胞均有Cx43mRNA及蛋白表达 ,且增殖活性下降 ,但凋亡不增加。结论 转染Cx43基因后的C6胶质瘤细胞致瘤性显著降低 ,且对荷载脑胶质瘤鼠具有明显的治疗作用 ,有可能成为恶性胶质瘤基因治疗的优选靶的之一。
Objective To investigate the effect of connexin (Cx) 4 3 gene on glioma growth inhibition. Methods C6 glioma cells (control group) with Cx43 gene deletion and C6 cells transfected with Cx43 cDNA (transfection group) were planted in the right caudate nucleus of SD rats. The C6 glioma mice bearing Cx43 cDNA In situ treatment (treatment group), and empty vector treatment as control (no-load group), 10 rats in each group. The general condition, survival time, MRI dynamic changes and pathological changes were observed. The expression of Cx43 mRNA and protein was detected by in situ hybridization and immunohistochemical staining. The proliferative activity was detected by AgNOR and the apoptosis was detected by Tunel method. Results Both the control group and the no-load group died within 3 weeks. Six rats in the transfection group and 8 rats in the treatment group were observed to have no natural death within 12 days. In addition to treatment group 1 only residual tumor, the remaining tumor disappeared. Cx43 mRNA and protein expression in the transfected and treated groups of tumor cells, and the proliferation activity decreased, but the apoptosis did not increase. Conclusion C6 glioma cells transfected with Cx43 gene have significantly reduced tumorigenicity and obvious therapeutic effect on glioma-bearing glioma mice, which may be one of the preferred targets for gene therapy of malignant glioma.