Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression
Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression
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DOI：
10.1097/gme.0b013e318156fb77
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发表时间：
2008-05
期刊：
影响因子：
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通讯作者：
Yoshihiro Tanaka;Kiyoko Kato;R. Mibu;S. Uchida;K. Asanoma;K. Hashimoto;M. Nozaki;N. Wake
中科院分区：
文献类型：
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作者：
Yoshihiro Tanaka;Kiyoko Kato;R. Mibu;S. Uchida;K. Asanoma;K. Hashimoto;M. Nozaki;N. Wake
目的：探讨醋酸甲羟孕酮对体外培养的结肠癌细胞的作用。设计：以人结肠癌细胞株HT29和HCT116为研究对象。通过细胞生长和WST-1实验观察醋酸甲羟孕酮的抗增殖作用。通过细胞周期分析，观察醋酸甲羟孕酮对细胞周期分布的影响。采用免疫印迹、免疫沉淀和细胞周期蛋白依赖性激酶分析等方法研究细胞周期蛋白水平的变化。结果：醋酸甲羟孕酮通过诱导G0/G1期积聚抑制癌细胞的增殖。醋酸甲羟孕酮降低细胞周期蛋白E的表达，增加p21WAF1/CIP1的表达，增强p21WAF1/CIP1与细胞周期蛋白依赖性蛋白激酶2的相互作用，最终抑制其活性。结论：醋酸甲羟孕酮通过调节细胞周期相关蛋白的表达和细胞周期蛋白依赖性蛋白2的活性发挥抗增殖作用。这些结果应该有助于阐明醋酸甲羟孕酮对结肠癌风险的保护作用。
Objective: To investigate the effects of medroxyprogesterone acetate on colon cancer cells in vitro. Design: HT29 and HCT116 human colon cancer cell lines were used in this study. Cell growth and WST-1 assays were performed to investigate the antiproliferative effect of medroxyprogesterone acetate. Cell cycle analysis was performed to investigate the effects of medroxyprogesterone acetate on cell cycle distribution. Western blot, immunoprecipitation, and a cyclin-dependent kinase assay were performed to investigate changes in the levels of cell cycle proteins. Results: Medroxyprogesterone acetate inhibited proliferation of the cancer cells by inducing accumulation in the G0/G1 fraction. Medroxyprogesterone acetate decreased expression of cyclin E, increased expression of p21WAF1/CIP1, and enhanced interaction of p21WAF1/CIP1 with cyclin-dependent kinase 2, eventually inhibiting its activity. Conclusions: Medroxyprogesterone acetate exerts its antiproliferative effect by modulating cell cycle-related protein expression and cyclin-dependent kinase 2 activity. These results should help to elucidate the protective effect of medroxyprogesterone acetate on colon cancer risk.