摘要
背景与目的:研究表明熊果酸(ursolicacid,UA)可抑制多种肿瘤细胞的增殖并诱导凋亡,但目前有关UA作用于胃癌细胞的报道较为少见。环氧合酶-2(cyclooxygenase-2,COX-2)在多种癌前病变及癌组织中高表达。本研究旨在探讨熊果酸抑制人胃癌细胞SGC7901增殖和诱导凋亡的机制。方法:MTT法检测0、10、20、30、40!mol/LUA作用不同时间对SGC7901细胞增殖的影响;荧光染料Hoechst33258染色观察不同浓度UA作用24h细胞凋亡情况;流式细胞仪检测细胞周期变化及凋亡率;Westernblot法检测COX-2蛋白以及凋亡相关蛋白Bcl-2、Bax表达。放射免疫分析法测定COX-2催化产物前列腺素E2(prostaglandinE2,PGE2)。结果:20~40!mol/LUA可抑制SGC7901细胞的增殖,并呈浓度和时间依赖性,作用12、24、36、48h的半数抑制浓度(IC50)分别为(57.50±1.18)!mol/L、(34.28±2.05)!mol/L、(27.54±1.11)!mol/L、(24.83±1.02)!mol/L;20~40!mol/LUA作用24h后,SGC7901细胞被阻滞于G0/G1期,细胞凋亡率分别为(9.10±2.39)%、(26.30±1.25)%、(35.20±2.26)%;同时COX-2蛋白表达及其催化生成产物PGE2浓度下降,凋亡相关蛋白Bcl-2表达减少,Bax无明显变化。结论:熊果酸对SGC7901细胞具有增殖抑制及诱导凋亡作用,其机制可能与阻滞细胞周期、抑制COX-2表达进而减少PGE2生成以及下调凋亡相关蛋白Bcl-2表达有关。
BACKGROUND & OBJECTIVE: Some studies have showed that ursolic acid (UA) can inhibit proliferation and induce apoptosis of many tumor cell lines, however its effect on gastric cancer cells has rarely been reported. Cyclooxygenase-2 (COX-2) is highly expressed in various precursor lesions and cancerous tissues. This study was to investigate the effect of UA on COX-2, Bcl-2 and Bax expression in human gastric cancer cell line SGC7901, and explore its potential mechanisms of inhibiting proliferation and inducing apoptosis. METHODS: MTT assay was used to observe the effect of UA (0, 10, 20, 30, 40μmol/L) on proliferation of SGC7901 cells. Cell apoptosis was observed by fluorescence microscopy when treated with UA for 24 h. Cell cycle and apoptosis were analyzed by flow cytometry (FCM). The expression of COX-2, Bcl-2 and Bax was detected by Western blot. The level of prostaglandin E2 (PGE2) was measured by radioimmunoassay (RIA). RESULTS: UA (20-40μmol/L) significantly inhibited the proliferation of SGC7901 cells in dose- and timedependent manners, the IC50 value of UA at 12 h, 24 h, 36 h, 48 h were (57.50±1.18)μmol/L, (34.28±2.05)μmol/L, (27.54±1.11) μmol/L, and (24.83+1.02) μmol/L, respectively. When treated with 20-40 μmol/L UA for 24 h, SGC7901 cells were arrested at Go/G1 phase, and the apoptosis rates were (9.10±2.39)%, (26.30±1.25)%, and (35.20±2.26)%, respectively; meanwhile, COX-2 expression and its catalysate PGE2 were decreased, Bcl-2 expression was also decreased, whereas Bax expression was unchanged. CONCLUSION: UA could inhibit proliferation and induce apoptosis of SGC7901 cells through arresting cell cycle, inhibiting COX-2 expression to reduce PGE2 production and down-regulate Bcl-2 expression.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2006年第4期432-437,共6页
Chinese Journal of Cancer
基金
湖北省教育厅基金资助项目(No.2001A14012)~~