Notch1参与调节胃癌顺铂耐药的机制  

The mechanism about DDP-resistant phenotype mediated by Notchl in gastric cancer

作　　者：李大卫[1] 彭志海[1] 吴晴[2] 李真真[2] 王静珏 杨海燕[2] 

机构地区：[1]上海交通大学附属第一人民医院普外科,200080 [2]上海交通大学附属第一人民医院肿瘤科,200080

出　　处：《中华实验外科杂志》2009年第1期28-30,共3页Chinese Journal of Experimental Surgery

基　　金：基金项目：上海市自然科学基金资助项目（03ZR14077）

摘　　要：目的探讨Notch1参与胃癌SGC7901／DDP细胞株顺铂耐药的机制。方法应用Notch1通路抑制剂MW167抑制Notch1在敏感株SGC7901和耐药株SGC7901／DDP中的表达，通过噻唑蓝（MTT）比色法检测药物敏感性，流式细胞术分析细胞凋亡率，逆转录-聚合酶链反应（RT-PCR）和Western blot检测敏感株SGC7901和耐药株SGC7901／DDP中Notch1和NF-kappa B（NF-κB），耐药蛋白P-糖蛋白（P-gP）的表达变化。结果MW167抑制Notch1表达后敏感株SGC7901和耐药株SGC7901／DDP的药物敏感性显著增加，细胞凋亡率分别为23．71％和12．48％（P〈0．01），NF-κB和耐药蛋白P-gP在基因和蛋白表达水平均明显减低（P〈0．01）。结论Notch1可通过调节P-gP表达及抗凋亡信号通路参与胃癌顺铂耐药，可成为逆转胃癌耐药的新的靶点。Objective To investigate the possible mechanism of DDP-resistant phenotype in gastric cancer cell line SGC7901/DDP mediated by Notch1. Methods The Notchl expression was blocked by the Notchl inhibitor MW167 in both the drug-sensitive cell line SGC7901 and the DDP-resistant cell line SGC7901/DDP. Then this study detected the drug sensitivity by MTT assay, apoptosis rate by flow cy- tometry, and the expression of NF-kappa B （NF-κB） and the muhidrug-resistant protein P-glycoprotein （P-gp） by RT-PCR and Western blot in both the mRNA and protein levels. Results The inhibition of Notchl by MW167 resulted in increased drug sensitivity of both SGC7901 and SGC7901/DDP cell lines, with apoptosis rate being 23.71% and 12.48% respectively, and also the down-regulation of NF-κB and P-gp in both mRNA and protein levels （P 〈 0.01 ）. Conclusion The Notchl mediated the DDP-resistant phenotype through P-gp expression and anti-apoptosis signal pathway in gastric cancer, which would be a novel and promising target gene for reversing MDR.

关 键 词：胃肿瘤 多药耐药 P糖蛋白 

分 类 号：R735.2[医药卫生—肿瘤]