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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
作者姓名:Ma XT  Yu LW  Wang S  Zhang H  Du RY  Cui ZR
作者单位:1. 100080,北京市海淀医院外科
2. 北京大学人民医院外科,外科肿瘤研究室
基金项目: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(COX-2)抑制剂NS-398对结肠癌细胞系SW480中Stats与PPAR8信号转导通路的影响,以期初步阐明选择性COX-2抑制剂抗结直肠癌非COX-2依赖性的作用机制。方法应用RT—PCR检测结肠癌细胞系SW480中COX-2 mRNA表达水平,用选择性COX-2抑制剂NS-398处理结肠癌细胞系SW480,Western印迹检测Stats与PPAR8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COX-2 mRNA表达,NS-398(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。Stats、PPAR8、细胞周期蛋白D1与Bcl—x1表达水平随NS-398作用时间延长而下降。结论选择性COX-2抑制剂NS-398可能通过非COX-2依赖途径影响结肠癌细胞的增殖。

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
收稿时间:2005-04-25
修稿时间:2005-04-25

Molecular mechanism of cyclooxygenase-2 inhibitor in inhibition of proliferation of colon cancer cells by modulating Stat5 signal transduction pathway
Ma XT,Yu LW,Wang S,Zhang H,Du RY,Cui ZR.Molecular mechanism of cyclooxygenase-2 inhibitor in inhibition of proliferation of colon cancer cells by modulating Stat5 signal transduction pathway[J].National Medical Journal of China,2005,85(36):2566-2569.
Authors:Ma Xiang-tao  Yu Li-wei  Wang Shan  Zhang Hui  Du Ru-yu  Cui Zhi-rong
Institution:Department of Surgery, Beijing Haidian Hospital, Beijing 100080, China. xiangtao_ma@pku.org.cn
Abstract: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 125 micromol/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 Stat5, peroxisome proliferators-activated receptors (PPARs), cyclin D1 and Bcl-x(L). RESULTS: Expression of COX-2 mRNA was not detected in the SW480 colon cancer cells. 72 hours after the addition of NS398 75 micromol/L the proliferative level of the SW480 cells was decreased; the rate of the cells at the G(1) 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 Stat5, PPARdelta, cyclin D1 and Bcl-x(L) 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.
Keywords:Colorectal neoplasms  Signal transduction  Apoptosis  Cyclooxygenase-2
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