摘要
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 study the role of connexin gene (Cx43) in the suppression of C6 glioma. Methods Cx43 gene depleted parental C6 rats (control group) and C6 cells transfected with Cx43 cDNA (transfection group) were implanted into the right caudate nucleus of SD rats. Rats bearing cerebral C6 gliomas were treated with Cx43 cDNA (treatment group) with another group treated with empty vector (empty vector group) serving as control. The general manifestation, survival time, MRI dynamic scanning and histopathological changes in all rats were observed. Cx43 mRNA and its protein were examined by in situ hybridization and immunohistochemistry. Proliferation activity was monitored by the average number of AgNOR stain. Cell apoptosis was examined by the Tolt-mediated x-duTP nick end labeling (TUNEL) method. Results All rats in the control and empty vector groups died of cerebral glioma within 3 weeks after implantation of C6 cells. Six in the transfection group and 8 in the treatment group were alive beyond 120 days with complete disappearance of the tumor foci, except one in this group having some residue of tumor. In the glioma of transfection and treatment groups, Cx43 gene expression was up-regulated, proliferation activity reduced while the apoptotic cells did not increase. Conclusion The development of glioma is greatly suppressed by the transfection of Cx43 gene, which has great effectiveness in rats bearing cerebral malignant gliomas. This could become a target of choice in the gene treatment of malignant gliomas.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2002年第3期212-214,共3页
Chinese Journal of Oncology
基金
国家自然科学基金资助项目 ( 39870 815 )
