曲古抑菌素A通过P38丝裂原激活蛋白激酶信号通路调节胃癌细胞水通道蛋白1的表达  

Effect of TSA on aquaporin-1 protein expression in gastric epithelial cancer cells through P38MAPK signal pathway

作　　者：孙维建[1] 胡丹红[1] 李丕宏[1] 卢明东[1] 吴昊[1] 周香[1] 林海鸿[1] 屠洋洋 俞耀军[1] 黄和[1] 周磊[1] 郑志强[1] 

机构地区：[1]温州医学院附属第二医院普外科,浙江省325000

出　　处：《中华普通外科杂志》2015年第7期548-552,共5页Chinese Journal of General Surgery

基　　金：温州市科技计划资助项目（Y20130281）;温州医科大学附属第二医院资助项目（2013A003）

摘　　要：目的探讨曲古抑菌素A（TSA）通过P38丝裂原激活蛋白激酶信号通路调节胃癌细胞水通道蛋白1（aquaporin1，AQP1）的表达。方法用不同浓度的TSA处理胃癌SGC-7901细胞，MTT法检测细胞增殖情况，光镜和透射电镜下观察形态学改变，免疫组化及Westernblot方法检测P38、磷酸化P38（p-P38）及AQP1的表达。实验分4组：对照组、TSA组、TSA＋SB203580（P38MAPK通路抑制剂）组、SB203580组。结果（1）胃癌SGC．7901细胞的胞质及胞膜中均有棕褐色AQP1的阳性染色。不同药物作用后，各组AQP1表达定位未见变化。（2）TSA能够抑制细胞增殖，随着药物浓度的增加和作用时间的延长抑制率逐渐增加。（3）不同浓度TSA作用5h后，各组胃癌细胞中总P38表达相比差异均无统计学意义（均P〉0．05），p-P38和AQP1表达水平比较差异均有统计学意义（均P〈0．05）。TSA作用的最适宜浓度为100nmol／L。（4）不同浓度SB203580作用5h后，胃癌细胞中总P38表达比较差异均无统计学意义（均P〉0．05）；p-P38和AQP1表达水平比较差异均有统计学意义（均P〈0．05）。SB203580作用的最适宜浓度为10μmol／L。（5）用SB203580预处理胃癌细胞株2h后加入TSA100nmol／L作用组与不经过SB203580预处理而直接加用TSA作用各组的p-P38和AQP1相比差异有统计学意义（P〈0．01）。结论TSA通过P38丝裂原激活蛋白激酶信号通路对胃癌细胞AQP1的表达起调控作用。Objective To investigate the effects of TSA on AQP1 in gastric cancer through P38MAPK signal pathway. Methods Gastric cancer SGC-7901 cells were treated with TSA, or SB203580 inhibitor of P38MAPK signal pathway. The proliferation was detected by MTT assay. The morphological changes were observed with light microscope and transmission electron microscope. The expression of P38MAPK and phosphorylated P38 was detected by Western-blot. SGC-7901 cells was randomly divided into control group, TSA group, TSA ＋ SB203580 group, and SB203580 group. Results （ 1 ） Brown staining of AQP1 was detected in both cell membrane and cytoplasm in each group. （2） TSA inhibits SGC-7901 growth in a dose-dependent and time-dependent manner. （3） After 5 hour TSA treatment the P38 expression did not vary among groups （ P 〉 0. 05 ）, while p-P38 and AQP1 protein expression significantly changed （ P 〈 0. 05）. （4） After 5 hours SB203580 treatment P38 expression did not vary among groups （P 〉 0. 05 ）, while p-P38 and AQP1 protein expression were significantly changed （ P 〈 0. 05）. （5） Pretreatment of SGC- 7901 cells with SB203580 lowered the level of p-P38 and AQP1 compared with controls （ P 〈 0. 01 ）. Conclusions TSA regulates AQP1 protein expression in human gastric cancer cell lines, possibly by a mechanism related to P38MAPK signal pathway.

关 键 词：胃肿瘤 水通道蛋白质1 丝裂原活化蛋白激酶类 

分 类 号：R411.9[医药卫生—临床医学]