【摘要】 目的:体外研究中药雄黄的主要成分硫化砷(As4S4)对子宫颈癌HeLa细胞的增殖抑制和诱导凋亡的作用及与环氧合酶-2(cyclooxygenase-2,COX-2)表达的关系。方法:以不同浓度的As4S4(7.5～60mg/L),分12～60h5个时间点处理HeLa细胞,四甲基偶氮唑蓝(MTT)法测定细胞增殖抑制率;DNA梯状电泳检测凋亡的发生;Western blot检测COX-2蛋白的表达;放射免疫法检测细胞前列腺素E2(prostaglandinE2,PGE2)释放水平。结果:As4S4可抑制HeLa细胞增殖,作用呈明显的时效和量效关系,P<0.01;As4S4可诱导HeLa细胞凋亡,DNA电泳呈梯状条带;As4S4可明显抑制COX-2的表达,P<0.01,并呈浓度依赖性;As4S4明显抑制HeLa细胞PGE2释放水平,其值分别为(70.56±2.03)、(48.58±2.28)、(29.25±1.57)和(18.02±1.04)μg/L,与对照组(83.15±1.01)μg/L比较差异有统计学意义,P<0.01。结论:As4S4体外对HeLa细胞具有增殖抑制和促进凋亡作用,其机制可能与抑制COX-2蛋白表达有关。更多还原

【Abstract】 OBJECTIVE:To investigate the HeLa cell growth inhibition and apoptosis induced by As4S4 and the relationship with COX-2 expression in vitro. METHODS: HeLa cells were treated with various concentrations (7.5-60 mg/L) of As4S4 for 12-60 h.The cell growth rate was measured by MTT; apoptosis was detected by DNA electrophoresis.The levels of PGE2 were measured by radioimmunoassay. The expression of COX-2 protein was also examined by Western blot analysis. RESULTS: After treated with different concentrations of As4S4, the cell growth of HeLa was suppressed significantly in dose and time-dependent manner in proliferative inhibition rate, P<0.01. As4S4 induced the apoptosis and DNA fragmentation gel analysis showed DNA ladder. As4S4 reduced the release of PGE2 in HeLa cells with the values being (70.56±2.03),(48.58±2.28),(29.25±1.57) and (18.02±1.04) μg/L, respectively, as compared with control group (83.15±0.01) μg/L, P<0.01. As4S4 inhibited the activity and expression of COX-2 with the rise of concentration, and it down-regulated the expression of COX-2 protein significantly. CONCLUSIONS: As4S4 can inhibit the proliferation and increase apoptosis in human HeLa cells. These effects may depend on the inhibition of the expression of COX-2 and level of PGE2 by As4S4.更多还原