胶质瘤中变异型IκBα的表达与抑制肿瘤浸润的研究  

Mutant-type IκBα down-regulating uPA and uPAR expression and inhibit tumor invasion in gliomas

作　　者：吴建梁[1] 于利洁[2] 扈玉华[1] 史学芳[1] 孔世奇[1] 尹风任[1] 冀建文[1] 范振增[1] 

机构地区：[1]河北医科大学第二医院神经外科,石家庄050000 [2]河北医科大学口腔医院病理研究室

出　　处：《中华神经外科杂志》2008年第11期830-833,共4页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金项目（30440016）;河北省自然科学基金项目（C2006000910）;河北省科技厅博士基金项目（06547009D-12）

摘　　要：目的探讨变异型IκBα（IκBαM）基因对人类多形性胶质母细胞瘤（GBM）细胞中尿激酶型纤溶酶原激活剂（urokinase type PA，uPA）和其受体（uPA—receptor，uPAR）表达的调控作用及其与肿瘤浸润行为的关系。方法构建质粒、基因转染以及IκBαM蛋白表达筛选，建立稳定表达IκBαM的人类GBM细胞株；用Transwell法测定肿瘤细胞的迁移能力；RT—PCR技术检测细胞内uPA、uPAR在RNA水平的表达；制作裸鼠皮下异位移植瘤生长模型，并采用免疫组化法分析肿瘤组织中uPA和uPAR的表达。结果Transwell法测定G36△—M组肿瘤细胞的迁移能力明显降低；RT—PCR及肿瘤组化染色结果显示，uPA和uPAR在G36△—M组中的表达显著低于G36△、G36△—W和G36△—P三组，而在后三组间的表达无统计学意义。结论IκBαM基因在RNA和蛋白水平均可显著降低人类恶性胶质瘤中uPA和uPAR的表达，进而减弱肿瘤细胞的浸润能力，抑制肿瘤组织的浸润。Objective This study was designed to investigate the regulation of mutant-type IκBα （IκBαM） to Urokinase type plasminogen activator （uPA） and its receptor （uPAR） in human glioblastoma multiform（GBM） cells, and the correlation to tumor invasion. Method Human GBM cell line was used, transfeeted with IκBαM gene and selected IκBαM protein＇s expression, to establish cell line which steadily express IκBαM protein. The invasive activity of tumor cells was assayed in a transwell cell culture chamber, and the expression of uPA and uPAR in RNA level were analyzed by RT-PCR method. The cells were injected subcutaneously into the nude mice, and then compare the expression of uPA and uPAR by immunohistochemistry method. Result Transwell data shows that the invasive activity of G36△-M group cells was lower than the other three groups. The expression of uPA and uPAR in RNA and protein levels were decrease significantly in G36△-M group in vitro and in vivo, but the other three groups （G36△-W, G36△-P and G36△） ahnost same. Conclusions IκBαM gene could down-regulate the expressions of uPA and uPAR in the human GBM cell line in protein level, and reduce the ability of tumor invasion.

关 键 词：核因子ΚB 变异型IκBα UPA UPAR TRANSWELL 

分 类 号：R686[医药卫生—骨科学]