The elucidation of MPA-induoed inhibition of colorectal cancer growth by hormone replace replacement therapy

通过激素替代疗法阐明 MPA 诱导的结直肠癌生长抑制作用

• 批准号: 18591836
• 负责人: MIBU Ryuichi
• 金额: $ 2.51万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591836/
• 关键词: MPA; Hormone Replacement Therapy; Colorectal Cancer; 更年期医学; 消化器学

Numerous epidemiological and experimental studies have suggested the possible effect of female sex hormones against colon cancer risk. The Women's Health Initiative recently reported data from a randomized controlled trial that compared estrogen plus progestin with placebo in postmenpausal women. In this report, therapy with a combination of conjugated equine estrogen(CEE) plus MPA was associated with a significant decrease in the incidence of colorectal cancer, while therapy with CEE alone neither increased nor decreased the incidence of colorectal cancer. However, the precise mechanism by which MPA prevents colorectal cancer remains to be fully investigated. To investigate the effects of medroxyprogesterone acetate on colon cancer cells in vitro, 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 cyclin-dependent kinase assay were performed to investigate changes in the levels of cell cycle proteins.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 p21, and enhanced interaction of p21 with cyclin-dependent kinase2, eventually inhibiting its activity. 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.

许多流行病学和实验研究表明，女性性激素可能对结肠癌风险产生影响。妇女健康倡议最近报道了一项随机对照试验的数据，该试验比较了绝经后妇女服用雌激素加孕激素和安慰剂的效果。在本报告中，结合马雌激素（CEE）加MPA联合治疗与结直肠癌发病率的显著降低相关，而单独使用CEE治疗既不增加也不减少结直肠癌的发病率。然而，MPA预防结直肠癌的确切机制仍有待充分研究。为探讨醋酸甲羟孕酮在体外对结肠癌细胞的作用，本研究采用人结肠癌细胞系HT 29和HCT 116。细胞生长和WST-1测定来研究醋酸甲羟孕酮的抗增殖作用。采用细胞周期分析法研究醋酸甲羟孕酮对细胞周期分布的影响。用Western blot、免疫沉淀和细胞周期蛋白依赖性激酶（cyclin-dependent kinase，cyclin-dependent kinase）检测细胞周期蛋白的变化，结果表明：醋酸甲羟孕酮通过诱导G 0/G1期细胞聚集而抑制癌细胞增殖。醋酸甲羟孕酮降低细胞周期蛋白E的表达，增加p21的表达，并增强p21与细胞周期蛋白依赖性激酶2的相互作用，最终抑制其活性。醋酸甲羟孕酮通过调节细胞周期相关蛋白表达和细胞周期蛋白依赖性激酶2活性发挥其抗增殖作用。这些结果有助于阐明醋酸甲羟孕酮对结肠癌风险的保护作用。

项目成果

The human HVMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice

人类 HVMAI/PLAGL1 差异甲基化区域充当小鼠的印记控制区域

• 发表时间: 2006
• 期刊: Genomics 88
• 作者: Arima;et. al.
• 通讯作者: et. al.

An inhibitory effect on cell proliferation by blockage of the MAPK/estrogen receptor/MDM2 signal pathway in gynecologic cancer.

• DOI: 10.1016/j.ygyno.2006.12.030
• 发表时间: 2007-05
• 期刊: Gynecologic oncology
• 影响因子: 4.7
• 作者: S. Suga;Kiyoko Kato;T. Ohgami;A. Yamayoshi;Sawako Adachi;K. Asanoma;S. Yamaguchi;T. Arima;K. Kinoshita;N. Wake

The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice

• DOI: 10.1016/j.ygeno.2006.07.005
• 发表时间: 2006-11-01
• 期刊: GENOMICS
• 影响因子: 4.4
• 作者: Arima, Takahiro;Yamasaki, Katsuhisa;Kono, Tomohiro
• 通讯作者: Kono, Tomohiro

Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression

• DOI: 10.1097/gme.0b013e318156fb77
• 发表时间: 2008-05
• 期刊: Menopause
• 作者: Yoshihiro Tanaka;Kiyoko Kato;R. Mibu;S. Uchida;K. Asanoma;K. Hashimoto;M. Nozaki;N. Wake

直腸癌を合併した放射性腸炎の一例

放射性肠炎并发直肠癌1例

• 发表时间: 2006
• 作者: 工藤暫司;ら
• 通讯作者: ら