环氧合酶-2抑制剂调控Stat5信号转导通路抑制结肠癌细胞增殖的分子机制  

Molecular mechanism of cyclooxygenase-2 inhibitor in inhibition of proliferation of colon cancer cells by modulating Stat5 signal transduction pathway

作　　者：马向涛[1] 余力伟[1] 王杉[2] 张辉[2] 杜如昱[2] 崔志荣[2] 

机构地区：[1]北京市海淀医院外科,100080 [2]北京大学人民医院外科外科肿瘤研究室

出　　处：《中华医学杂志》2005年第36期2566-2569,共4页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30271269)

摘　　要：目的观察选择性环氧合酶2(COX2)抑制剂NS398对结肠癌细胞系SW480中Stat5与PPARδ信号转导通路的影响,以期初步阐明选择性COX2抑制剂抗结直肠癌非COX2依赖性的作用机制。方法应用RTPCR检测结肠癌细胞系SW480中COX2mRNA表达水平,用选择性COX2抑制剂NS398处理结肠癌细胞系SW480,Western印迹检测Stat5与PPARδ信号转导通路成员表达,四甲基偶氮唑盐(MTT)法检测细胞增殖状态,流式细胞技术检测细胞周期与凋亡情况。结果结肠癌细胞系SW480中未检测到COX2mRNA表达,NS398(75μmol/L)作用于SW480细胞72h后,G1期细胞比率由31.2%上升至40.6%,S期细胞比率由52.8%下降至41.2%,细胞增殖受抑制。Stat5、PPARδ、细胞周期蛋白D1与BclxL表达水平随NS398作用时间延长而下降。结论选择性COX2抑制剂NS398可能通过非COX2依赖途径影响结肠癌细胞的增殖。Objective To investigate the role of NS398, a selective cyclooxygenase （COX）-2 inhibitor, in proliferation and apoptosis of colorectal cancer, and to reveal the mechanism of inhibiting colon cancer by NS-398 Independent of COX-2. Methods Human colon cancer cells of the line SW480 were cultured and then divided into 2 groups ： experimental group and control group. NS398 of the concentrations of 12,5, 25, 50, 75, 100, and 125μmol/L was added into the culture fluid of the experimental group. MTT assay was used to observe the proliferation of the cells, flow cytometry was used to test the cell cycle, RT-PCR analysis was performed to examine COX-2 mRNA expression, and Western blotting analysis was performed to detect the expression of StatS, peroxisome proliferators-activated receptors （PPARs） , cyclin D1 and Bcl-xL. Results Expression of COX-2 mRNA was not detected in the SW480 colon cancer cells, 72 hours after the addition of NS398 75 g, mol/L the proliferative level of the SW480 cells was decreased; the rate of the cells at the G1 stage increased from 31.2% to 40, 6% , and the rate of cells at the S stage decreased from 52, 8% to 41.2%, The expression of StatS, PPARS, cyclin D1 and Bcl-xL decreased along with the elongation of time of NS398 action. Conclusion COX-2 inhibitor, such as NS-398 inhibits the colon cancer cell proliferation and induces apoptosis of colon cancer cells with the possible mechanism of inhibiting the proliferation and inducing the apoptosis of colon cancer cells through a pathway independent of COX-2,

关 键 词：结肠直肠肿瘤 信号传递 脱噬作用 环氧合酶-2 环氧合酶-2抑制剂 结肠癌细胞系 信号转导通路 癌细胞增殖 选择性COX-2抑制剂 STAT5 

分 类 号：R735.35[医药卫生—肿瘤]