Effect of mifepristone on proliferation and apoptosis of Ishikawa endometrial adenocarcinoma cells
Effect of mifepristone on proliferation and apoptosis of Ishikawa endometrial adenocarcinoma cells
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DOI：
10.1016/j.fertnstert.2005.01.126
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发表时间：
2005-07-01
影响因子：
6.7
通讯作者：
Jain, JK
中科院分区：
文献类型：
--
作者：
Li, AM;Felix, JC;Jain, JK
目的：探讨米非司酮改善突破性出血的机制，探讨在黄体酮存在和不存在的情况下，米非司酮对石川子宫内膜癌细胞增殖和凋亡的影响。设计：前瞻性基础研究。环境：一所大学医学院的生殖健康研究实验室。病人:没有。干预：石川细胞体外培养。在细胞中加入不同浓度的米非司酮和/或醋酸甲孕酮。主要观察指标：细胞增殖和凋亡的测定。结果：比色法3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑和溴脱氧尿苷（BrdU）标记分析表明，米非非酮抑制石川细胞的生长和BrdU标记细胞的百分比，并呈时间和剂量依赖性。流式细胞术分析表明，100 μ mol/L米非司酮完全抑制细胞增殖，S期细胞比例增加，G(2)/M期细胞比例减少。凋亡通过annexin- v -异硫氰酸荧光素结合和caspase-3激活来鉴定。免疫荧光双标记石川细胞在没有或有米非司酮的情况下显示BAX蛋白表达增加，并从细胞质转移到线粒体。结论：米非司酮通过阻滞细胞s期周期进程，激活caspase-3诱导细胞凋亡，调节石川细胞凋亡调控基因BCL2/BAX和FAS/FASLG抑制细胞生长。总之，这些数据表明，米非司酮治疗突破性出血的改善可能是由于子宫内膜组织体积的减少，这与子宫内膜萎缩相似。(c) 2005年，美国生殖医学学会。
Objective: To determine the mechanism by which mifepristone improves breakthrough bleeding, the effects of mifepristone on proliferation and apoptosis of Ishikawa endometrial carcinoma cells were evaluated in the presence and absence of progestin.Design: Prospective basic research study.Setting: Research laboratories for reproductive health at a university medical school.Patient(s): None. Intervention(s): Ishikawa cells were cultured in vitro. Mifepristone and/or medroxyprogesterone acetate at various concentrations were added to the cells.Main Outcome Measure(s): Determination of cell proliferation and apoptosis.Result(s): Colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine (BrdU) labeling analysis demonstrated that mifepristone inhibited the growth of Ishikawa cells and percentage of BrdU-Iabeled cells in a time- and dose-dependent manner. Flow cytometry analysis demonstrated that mifepristone at 100 mu mol/L, which completely inhibited cell proliferation, increased the proportion of cells in the S phase and diminished the cells in the G(2)/M phase. Apoptosis was identified by annexin-V-fluorescein isothiocyanate binding and caspase-3 activation. Immunofluorescent double labeling of Ishikawa cells in the absence or presence of mifepristone revealed that BAX protein expression increased and translocated from cytosol to mitochondria.Conclusion(s): Mifepristone inhibited cell growth by arresting cell cycle progression at S phase, induced apoptosis through caspase-3 activation, and modulated apoptosis regulatory genes BCL2/BAX and FAS/FASLG in Ishikawa cells. Together, these data imply that the improvement in breakthrough bleeding observed with mifepristone might be due to diminished volume of endometrial tissue similar to that seen with endometrial atrophy. (c) 2005 by American Society for Reproductive Medicine.