中国药物警戒 ›› 2018, Vol. 15 ›› Issue (9): 533-536.

• 垂体肿瘤治疗靶点及药物专栏 • 上一篇    下一篇

地西他滨治疗垂体库欣病的体外研究

张莉1, 张洪霞2   

  1. 1济南市第二人民医院药学部,山东 济南 250001;
    2山东大学齐鲁儿童医院肾脏风湿免疫科,山东 济南 250022
  • 收稿日期:2018-11-02 修回日期:2018-11-02 出版日期:2018-09-20 发布日期:2018-11-02
  • 作者简介:张莉,女,硕士,副主任药师,内分泌临床药理。

Effects of Decitabine on Pituitary-dependent Cushing's Disease in vitro

ZHANG Li1, ZHANG Hongxia2   

  1. 1Department of Pharmacy, Jinan Second People's Hospital, Shandong Jinnan 250001, China;
    2Department of Kidney and Rheumatic Immunology, Qilu Children's Hospital of Shandong University, Shandong Jinan 250022, China
  • Received:2018-11-02 Revised:2018-11-02 Online:2018-09-20 Published:2018-11-02

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摘要： 目的 观察地西他滨对垂体促肾上腺皮质激素（adreno-cortico-tropic-hormone, ACTH）腺瘤AtT-20细胞增殖、凋亡和激素分泌的影响。方法 AtT-20细胞分为地西他滨组和对照组,地西他滨组分别给予不同浓度地西他滨 （1、5、10 μM)处理,对照组给予等体积二甲基亚砜（DMSO）。细胞增殖试验（MTS法）检测药物干预24、48、72 h细胞增殖活力的变化。流式细胞仪分析经Annexin V-FITC/PI双染后细胞凋亡水平,Real-time PCR检测凋亡相关基因Bax、Bcl-2的表达。ELISA检测药物处理后细胞分泌ACTH的水平变化。结果 与对照组相比,不同浓度的地西他滨组处理后,AtT-20细胞增殖活力和ACTH分泌能力显著下降,并表现出了良好的时间和浓度依赖关系。药物处理72 h后,地西他滨组细胞凋亡率显著上升。凋亡相关基因Bax表达显著上调,Bcl-2基因表达显著下降,差异具有统计学意义（P <0.05）。结论 地西他滨可以诱导AtT-20细胞凋亡并抑制细胞增殖和分泌ACTH,地西他滨在垂体库欣病中具有潜在治疗作用。

关键词: 地西他滨, 垂体库欣病, ACTH, AtT-20细胞, 细胞增殖

Abstract: Objective To observe the effects of decitabine on the proliferation, apoptosis and hormone secretion of adrenocorticotropic hormone (ACTH) pituitary adenoma AtT-20 cells. Methods The drug groups were given different concentrations of decitabine(1, 5, 10 μM), and control group was given equal volume of dimethyl sulfoxide (DMSO). The proliferation of AtT-20 cells was determined by MTS test after treated with different concentrations of decitabine for 24, 48, 72 h, and the apoptosis levels were measured by Annexin V/PI. Simultaneously, ACTH secretion ofAtT-20 cells by ELISA and the mRNA expression of apoptosis related genes such as Bax and Bcl-2 by Real-time PCR were detected. Results Compared with control group, decitabine could effectively inhibit the proliferation and ACTH secretion of AtT-20 cells in a concentration-dependent and time-dependent manner. After 72 h treatment, the apoptosis cells in decitabine groups were significantly increased. And the levels of Bax were increased and expressions of Bcl-2 mRNA were statistically decreased in decitabine groups than that of control group (P <0.05). Conclusion Decitabine can induce apoptosis of AtT-20 cells and inhibit cell proliferation and ACTH secretion. Decitabine might have a potential protective effect on pituitary-dependent Cushing's disease.

Key words: decitabine, pituitary-dependent Cushing's disease, ACTH, AtT-20 cells, proliferation

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