GSK-3β抑制剂对结肠癌SW480细胞增殖和凋亡的影响  

Effects of GSK-3β inhibitor on proliferation and apoptosis of SW480 cells

作　　者：刘坤平[1,2] 钟雪云[3] 罗枫 赵彤[1] 

机构地区：[1]南方医科大学南方医院病理科,广东广州510515 [2]暨南大学医学院附属清远医院病理科,广东清远511500 [3]暨南大学医学院病理学教研室,广东广州510632

出　　处：《中国病理生理杂志》2011年第1期97-101,共5页Chinese Journal of Pathophysiology

基　　金：广东省科技计划资助项目(No.2009B080800023)

摘　　要：目的:探讨糖原合成酶激酶3β(GSK-3β)抑制剂(2 Z,3 E)-6-溴靛-3-肟(BIO)对结肠癌SW480细胞β-catenin、Bcl-2蛋白表达及细胞周期、凋亡的影响。方法:应用不同浓度BIO作用于结肠癌SW480细胞,采用流式细胞术检测细胞周期及凋亡,Western blotting检测β-catenin和Bcl-2蛋白表达,免疫细胞化学检测β-catenin及cyclin D1的表达,HE染色观察细胞形态。结果:与BIO处理前SW480细胞相比,BIO处理组SW480细胞β-catenin蛋白表达明显上调并出现部分细胞核移位,cyclin D1蛋白表达及S期和G2/M期细胞不同程度增多,Bcl-2蛋白表达有所下调,细胞凋亡率明显下降,并出现细胞形态改变。结论:GSK-3β抑制剂BIO作用于结肠癌SW480细胞呈现促增殖及抑凋亡作用,其机制主要与β-catenin信号转导通路激活以及与Bcl-2调控通路的平衡有关,其中β-catenin上调可能是影响结肠癌SW480细胞转归的主要因素。AIM：To investigate the mechanism and the effect of glycogen synthase kinase 3β（GSK-3β） inhibitor（2＇Z,3＇E）-6-bromoindirubin-3＇-oxime（BIO） on the protein expression of β-catenin and Bcl-2,and proliferation and apoptosis in colon carcinoma SW480 cells.METHODS：The immunohistochemical staining and Western blotting were performed to detect the protein expression of β-catenin,cyclin D1 and Bcl-2.The cell cycle distribution and apoptotic rate were detected by flow cytometry.The morphologic features of SW480 cells before and 24 h after BIO exposure at different concentrations were observed under microscope with HE staining.RESULTS：Compared with the untreated SW480 cells,the protein expression of β-catenin significantly increased and some β-catenin positive nuclear staining positive cells appeared in BIO treated cells.and The cells exposed to BIO showed that the cyclin D1 protein and the cells in S stage and G2/M stage moderately increased,the protein level of Bcl-2 moderately decreased,and the cell apoptosis rate was significantly lower than those in control cells.Furthermore,the morphological changes of the SW480 cells were observed 24 h after BIO treatment.CONCLUSION：Our results indicate that GSK-3β inhibitor BIO participates in the cellular processes of promoting proliferation and inhibiting apoptosis in colon carcinoma cells.The mechanisms are mainly associated with activating the β-catenin pathway and regulating the balance of Bcl-2 pathway,and the up-regulation of β-catenin is most likely the possible factor for SW480 cell regression.

关 键 词：结直肠肿瘤 糖原合酶激酶3Β Β-CATENIN BCL-2 细胞增殖 细胞凋亡 

分 类 号：R735.3[医药卫生—肿瘤]