环氧化酶-2选择性抑制剂抑制人食管癌细胞的生长及其诱导凋亡  

Effects of cyclooxygenase-2 selective inhibitor NS-398 on the proliferation and apoptosis of human esophageal carcinoma cell lines

作　　者：金春亭[1] 鲁蓓[2] 李海军[1] 李玉珍[1] 武欣[1] 范婕[1] 张林西[1] 

机构地区：[1]河北北方学院医学院病理学教研室,河北省张家口市075029 [2]河北北方学院附属第二医院普外科,河北省张家口市075100

出　　处：《世界华人消化杂志》2007年第5期440-446,共7页World Chinese Journal of Digestology

基　　金：河北省自然科学基金资助课题;No.C2005000664~~

摘　　要：目的:探讨NS-398对食管癌细胞的生物学效应及可能的作用机制.方法:常规方法培养食管癌Eca-109和TE-13细胞,以不同浓度NS-398(5,10,20,40,80μmol/L)处理24,48,72h.采用四甲基唑蓝法(MTT)检测NS-398对Eca-109和TE-13细胞生长的抑制作用;流式细胞仪(FCM)检测细胞凋亡及COX-2,Bcl-2,Bax蛋白的表达;TUNEL法检测2种细胞凋亡情况;用放射免疫分析(RIA)检测培养液上清中前列腺素E2(PGE2)含量.结果:NS-398可抑制2种细胞的生长,并随药物浓度的增高及作用时间的延长抑制率逐渐增高,并使2种细胞产生的PGE2明显降低.NS-398使2种细胞G0/G1期细胞显著增多,S期细胞显著减少(Eca-109:F=22.39,P<0.01;TE-13:F=46.99,P<0.01),并引起了明显的细胞凋亡.NS-398使2种细胞COX-2和Bcl-2表达显著减少,而Bax表达显著增高.COX-2和Bcl-2的表达呈显著正相关(Eca-109:r=0.925,P<0.01;TE-13:r=0.925,P<0.01),COX-2和Bax表达呈显著负相关(Eca-109:r=-0.937,P<0.01;TE-13:r=-0.703,P<0.01)、Bax和bcl-2表达呈显著负相关(Eca-109:r=-0.926,P<0.01;TE-13:r=-0.753,P<0.01).结论:NS-398可抑制食管癌细胞的增殖并可诱导其凋亡,应用COX-2选择性抑制剂对食管癌进行化学预防或辅助治疗具有可能性.AIM： To investigate the biological effects of NS-398, a cyclooxygenase-2 （COX-2） selective inhibitor, on esophageal carcinoma cell lines and the possible mechanism. METHODS： Esophageal carcinoma cell lines Eca-109 and TE-13 were cultured by routine method, and then treated with different concentrations of NS-398 （5, 10, 20, 40, and 80 μmol/L） for 24, 48 and 72 hours. The growths of Eca-109 and TE-13 cells were measured by MTT assay. The expression of COX-2, Bcl-2 and Bax in the cells were detected by flow cytometry （FCM）. TUNEL and FCM methods were also used todetect the NS-398-induced apoptosis of the cells. The content of prostaglandin E2 in the supernatants of cell culture was measured by radioimmunoassay （RIA）. RESULTS： NS-398 inhibited the proliferations of Eca-109 and TE-13 cells in concentration-and time-dependent manners, and also decreased the production of PGE2. Meanwhile, NS-398 treatment resulted in an increase of G0/G1-phase cells and a decrease of S-phase ones in both kinds of cells （Eca-109： F = 22.39, P 〈 0.01; TE-13： F = 46.99, P 〈 0.01）. The apoptosis of Eca-109 and TE-13 cells was also obviously increased after NS-398 treatment. COX-2 and Bcl-2 protein expression were down-regulated, while Bax protein expression was up-regulated in Eca-109 and TE-13 cells after NS-398 treatment. There was a positive correlation between COX-2 and Bcl-2 expression in the two cell lines （Eca-109： r = 0.925, P 〈 0.01; TE-13： r = 0.925, P 〈 0.01）, but a negative correlation between COX-2 and Bax expression （Eca-109： r = -0.937, P 〈 0.01; TE-13： r = -0.703, P 〈 0.01） as well as between Bax and Bcl-2 expression （Eca-109： r = -0.926, P 〈 0.01; TE-13： r = -0.753, P 〈 0.01）. CONCLUSION： COX-2 selective inhibitor NS-398 may inhibit the proliferation and induce the apoptosis of esophageal carcinoma cell lines through the inactivation of COX-2, down-regulation of Bcl-2 expression, and up-regulation of Bax experssion. It may be used in the chemopr

关 键 词：食管癌 ECA-109细胞 TE-13细胞 凋亡 增殖 环氧化酶-2 四甲基唑蓝法 流式细胞术 放射免疫分析 

分 类 号：R735.1[医药卫生—肿瘤]