转染nm23-H_1基因靶向阻断人大细胞肺癌细胞株L9981 Wnt信号传导通路  

Targeting blockage of Wnt signal transduction pathway of nm23-H1 gene transfection in human high-metastatic large cell lung cancer cell line L9981

作　　者：付军科[1,2] 周清华[1] 朱文[1] 王艳萍[1] 刘伦旭[1] 陈小禾[1] 聂强[1] 李定彪[1] 李印[1] 

机构地区：[1]四川大学华西医院四川省肺癌分子重点实验室,胸心外科,成都现在610041 [2]西安交通大学第一医院胸外科

出　　处：《中国肺癌杂志》2004年第4期294-297,共4页Chinese Journal of Lung Cancer

基　　金：国家自然科学基金 (No .30 0 70 333和No.30 1 0 0 0 75)资助~~

摘　　要：目的　探讨nm2 3 H1 基因转染靶向阻断人高转移大细胞肺癌细胞株L9981Wnt信号传导通路的可行性 ,为阐明nm2 3 H1 基因调控肺癌转移抑制的分子机制和靶向治疗提供实验依据。方法　以转染nm 2 3 H1 基因的L9981 nm 2 3 H1 、原代L9981、空载L9981 pLXSN三株人高转移大细胞肺癌细胞为研究对象 ,应用Westernblot检测比较各株肺癌细胞胞浆、胞核中Wnt信号传导通路关键激酶GSK 3 β和 β 连环蛋白表达的变化。结果　①GSK 3 β在L9981 nm 2 3 H1 肺癌细胞胞浆中表达量IOD( 63 41± 5 41)显著高于L9981( 373 6± 2 98)和L9981 pLXSN( 3 613± 3 83 ) (P <0 .0 0 1) ;②GSK 3 β在L9981 nm2 3 H1 肺癌细胞胞核中表达量IOD( 4 3 5 6± 490 )显著高于L9981( 65 7± 5 7)和L9981 pLXSN ( 70 5± 75 ) (P <0 .0 0 1) ;③β 连环蛋白在L9981 nm 2 3 H1 肺癌细胞胞浆中表达量IOD( 3 64 9± 118)显著高于L9981( 14 0 1± 3 1)和L9981 pLXSN ( 13 5 0± 5 5 )(P <0 .0 0 1) ;④β 连环蛋白在L9981 nm 2 3 H1 肺癌细胞胞核中表达量IOD( 2 945± 68)与L9981( 2 60 4± 2 3 )和L9981 pLXSN( 2 65 2± 5 3 )比较无显著性差异 (P >0 .0 5 ) ;⑤L9981与L9981 pLXSN两者间GSK 3 β和β 连环蛋白在肺癌细胞胞浆和胞核的?Objective To explore the possibility of targeting blockage of Wnt signal transduction pathway of nm23 H1 gene transfection in human high metastatic large cell lung cancer cell line L9981, and to provide evidence to elucidate the signal conductive mechanism of nm23 H1 mediated tumor metastasis suppression. Methods The expression of GSK 3β and β catenin of Wnt signal pathway was detected in cytoplasm and nucleus in L9981 cell line with nm23 H1 deletion, L9981 pLXSN cell line transfected with vector and L9981 nm23 H1 cell line transfected with nm23 H1 gene by Western blot. Results ①GSK 3β expression in L9981 nm23 H1 cytoplasm (6 341±541) was significantly higher than those in L9981 (3 736±298) and L9981 pLXSN (3 613±383) cell lines ( P <0.001); ②GSK 3β expression in L9981 nm23 H1 nucleus (4 356±490) was significantly higher than those in L9981 (657±57) and L9981 pLXSN (705±75) cell lines ( P <0.001); ③β catenin expression in L9981 nm23 H1 cytoplasm (3 649±118) was significantly higher than those in L9981 (1 401±31) and L9981 pLXSN (1 350±55) cell lines ( P <0.001); ④No statistical difference of the β catenin expression in nucleus was observed among L9981 nm23 H1 (2 945±68), L9981 (2 604±23) and L9981 pLXSN (2 652±53)( P >0.05); ⑤No significant difference of GSK 3β or β catenin expression in cytoplasm and nucleus was observed between L9981 and L9981 pLXSN ( P >0.05). Conclusion ①nm23 H1 gene can remarkably upregulate the expression of GSK 3β in cytoplasm and nucleus, and β catenin expression in cytoplasm in L9981 nm23 H1 cell, but can not induce the nucleus accumulation of β catenin. ②Regulation of GSK 3β and β catenin expression, and targeting blockage of Wnt signaling pathway may be one of molecular mechanisms that nm23 H1 contributes to play a vital role in the “Lung Cancer Metastasis Suppressive Cascade”.

关 键 词：L9981 nm-23-H1基因 GSK-3Β Β-连环蛋白 Wnt信号通路 分子靶向阻断 

分 类 号：R734.2[医药卫生—肿瘤]