ATP竞争性GSK-3抑制剂对人食管鳞癌细胞多药耐药的影响  

Effects of ATP-competitive GSK-3 inhibitor on multidrug resistance of human esophageal squamous-cell carcinoma cells

作　　者：甘思远[1] 钟雪云[2] 谢思明[2] 罗枫[3] 

机构地区：[1]广东医学院病理学教研室,广东湛江524023 [2]暨南大学医学院病理学教研室,广东广州510632 [3]清远市人民医院病理科,广东清远511518

出　　处：《中国病理生理杂志》2012年第7期1219-1223,共5页Chinese Journal of Pathophysiology

基　　金：国家863重大项目课题子课题(No.2006AA02A403)

摘　　要：目的:研究ATP竞争性糖原合成酶激酶3(GSK-3)抑制剂6-溴靛玉红-3'-肟(BIO)作用于食管鳞癌细胞后,对ATP结合盒(ABC)转运蛋白——P-糖蛋白(P-gp)和多药耐药相关蛋白2(MRP2)、凋亡抑制蛋白Bcl-2以及β-catenin表达的影响,探讨它们表达的相互关系,以及对细胞内游离ATP水平和P-gp、MRP2转运功能的影响,进而初步探讨GSK-3抑制剂对食管鳞癌细胞多药耐药的影响。方法:BIO作用于食管鳞癌EC-109细胞后,运用免疫荧光细胞化学法、流式细胞术以及ATP检测试剂盒分别检测细胞内MRP2、P-gp、β-cate-nin和Bcl-2表达的改变、ABC转运蛋白的转运功能以及细胞内游离ATP水平的改变。结果:BIO作用食管鳞癌EC-109细胞后,加药组与对照组相比,β-catenin和Bcl-2在胞浆中的表达增强,并且β-catenin出现胞核内累积,MRP2在胞浆和胞膜中表达增强,P-gp在胞浆和胞膜中表达减弱;细胞内游离ATP水平增加;ABC转运蛋白的转运功能增强。结论:BIO处理食管鳞癌细胞后增强了细胞的多药耐药。AIM： To study the changes and correlations of 13 -catenin, multidrug resistance -associated pro- tein 2 （MRP2）, P- glycoprotein （P-gp）, Bcl -2 and the free ATP level in esophageal squamous -cell carcinoma （ES- CC） cell line EC - 109 induced by ATP - competitive glycogen synthase kinase （ GSK - 3 ） inhibitor 6 - bremoindirubin - 3 ＇- oxime （BIO）. METHODS： The methods of flow cytometry, immunolluorescence, cytochemistry and ATP assay were used to study the expression levels of MRP2, P - gp, β - catenin and Bcl - 2, the efllux capability of ATP - binding cas- sette （ABC） transporters, and the free ATP level in ESCC cells. RESULTS： After induced by BIO, up - regulation of - catenin and Bcl - 2 expression in cytoplasm and accumulation of β - catenin in nucleus were found in ESCC ceils. The expression of MRP2 was up - regulated in cytoplasm and cell membrane. On the contrary, the expression of P - gp was down- regtdated in cytoplasm and cell membrane. The free ATP level and the efflux capability of ABC transporters in- creased in ESCC cells. CONCLUSION： The multidrug resistance of ESCC cells in enhanced by BIO treatment.

关 键 词：食管肿瘤 多药耐药 糖原合成酶激酶3 

分 类 号：R329.21[医药卫生—人体解剖和组织胚胎学]