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环氧合酶-2选择性抑制剂NS-398抑制肿瘤细胞的作用机制 预览 被引量:2

Inhibitory effects of a cyclooxygenase -2 inhibitor, NS398, on cancer cells
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摘要 目的:探讨COX-2选择性抑制剂NS-398对肿瘤细胞抑制的作用机制。方法:选择持续表达COX-2的人食管癌细胞株EC9706和不表达COX-2的肝癌细胞株SMMC7721作为研究对象,采用[^3H]-TdR掺入法检测不同浓度(10、20、50、100μmoL/L)NS-398和作用24h、48h、72h对细胞的增殖抑制效应;流式细胞术(FCM)及DNA片段分析法检测NS-398诱导的细胞凋亡情况;免疫细胞化学方法检测NS-398作用后细胞内survivin表达变化。结果:经不同浓度的NS-398处理,EC9706及SMMC7721的[^3H]-TdR掺入量均明显少于空白对照组(P〈0.05或P〈0.01),具有时间和剂量-效应关系。FCM检测发现EC9706在G.期前出现亚倍体凋亡峰,细胞凋亡率达(45.23±1.08)%,并出现典型的细胞凋亡梯带;而SMMC7721无凋亡峰出现,细胞凋亡率为(3.05±0.15)%,两组比较有显著性差异(P〈0.01)。经100μmoL/LNS398作用24h后,EC9706细胞内survivin表达与未经NS-398作用的EC9706细胞表达明显减少,而SMMC7721表达无变化。结论:NS398通过不同作用机制对肿瘤细胞发挥抑制作用,对COX-2表达阳性的肿瘤细胞具有诱导凋亡作用,与抑制survivin表达有关,而对无表达COX-2的肿瘤细胞无诱导凋亡作用。 AIM: To study the mechanism of growth inhibitory effect of a selective cyclooxygenase -2 (COX- 2) inhibitor, NS- 398, on cancer cells. METHODS: The esophageal cancer cell line (EC9706), which expresses COX- 2 constitutively, and hepatocellular carcinoma cell line (SMMC7721), which expresses no COX -2, were studied. The cell lines were incubated with NS - 398 at doses of 10, 20, 50, 100 μmol/L for 24 h, 48 h and 72 h. Antiproliferation effect was measured by [ ^3H ] -TdR incorporation. The cell apoptosis were determined by flow cytometry (FCM) and DNA fragmentation analysis. Survivin was detected by immunocytochemical technique. RESULTS: The growth inhibition was induced by NS398 in a dose - and time - dependent manners in both cell lines. FCM analysis revealed a high sub - G1 cell peak in EC9706 group and agarose electrophoresis showed marked apoptosis ladder pattern. However, no apoptosis was observed in SMMC7721 cells treated with NS- 398. The difference of apoptosis percentage in EC9706 and SMMC7721 was (45.23 ± 1.08) % and (3.05 ± 0. 15 ) % (P 〈 0. 01 ). After 24 h incubation with NS - 398 at concentration of 100 μmol/L, the expression of survivin was markedly reduced in EC9706, no change was observed in SMMC7721. CONCLUSION: NS -398 suppresses cell growth in cancer cell lines by different mechanism. NS -398 suppresses cell growth and increases apoptosis in the cancer cells that expresses COX -2.
作者 吴清明 李胜保 童强 王小虎 王强 WU Qing - ming, LI Sheng - bao, TONG Qiang, WANG Xiao - hu, WANG Qiang ( Department of Gastroenterology, Taihe Hospital, Yunyang Medical College, Shiyan 442000, China.)
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2006年第11期 2231-2234,共4页 Chinese Journal of Pathophysiology
基金 湖北省自然科学基金资助项目(No.2004ABA249) 湖北省科技厅攻关项目(No.2004AA304B)
关键词 环加氧酶抑制药 肿瘤 细胞增殖 细胞凋亡 Cyclooxygenase inhibitors Neoplasms Proliferation Apoptosis
作者简介 Tel:0719—8801593;E—mail:wuhe9224@sina.com
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参考文献12

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