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活性氧物种在偏钒酸钠对人前列腺癌细胞DU145增殖抑制中的作用

刘曈彤, 刘彦君, 杨晓改*   

  1. 北京大学医学部 药学院 化学生物学系, 北京 100191
  • 收稿日期:2011-05-30 修回日期:2011-10-10 出版日期:2012-01-01 发布日期:2012-01-01
  • 通讯作者: 杨晓改*

Role of reactive oxygen species in the antiproliferative effects of metavanadate on human prostate cancer DU145 cells

Tong-Tong Liu, Yan-Jun Liu, Xiao-Gai Yang*   

  1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191
  • Received:2011-05-30 Revised:2011-10-10 Online:2012-01-01 Published:2012-01-01
  • Contact: Xiao-Gai Yang*

摘要: 为研究偏钒酸钠对人前列腺癌细胞DU145的增殖抑制作用及其机制, 我们检测了偏钒酸钠对细胞活力、细胞周期、活性氧水平和细胞周期调节蛋白活性的影响。结果显示偏钒酸钠能显著降低调控Cdc2的主要磷酸酯酶Cdc25C的蛋白水平, 导致Cdc2 Tyr-15位磷酸化水平升高, 引起DU145细胞发生G2/M周期阻滞和增殖活力抑制。而抗氧化剂N-乙酰半胱氨酸能降低偏钒酸钠诱导升高的活性氧水平并能恢复偏钒酸钠导致的Cdc25C蛋白水平降低和Cdc2磷酸化水平(Tyr-15)的升高。这证实偏钒酸钠能导致DU145细胞发生G2/M周期阻滞从而引起细胞增殖活力抑制, 且这种抑制可能是通过偏钒酸钠所诱导的活性氧水平升高引起的Cdc25C蛋白降解实现的。

关键词: 偏钒酸钠, G2/M周期阻滞, Cdc25C, 活性氧物种

Abstract:

In the present study, the effects of metavanadate on the human prostate cancer cell line DU145 and the underlying mechanism were investigated. The results showed that metavanadate can cause cell cycle arrest at G2/M phase which was evidenced by cell cycle analysis and the increased phosphorylation of Cdc2 at its inactive Tyr-15 site. In addition, the results showed that metavanadate can induce reactive oxygen species (ROS) elevation and decrease the level of Cdc25C. This process can be rescued by an antioxidant, N-acetyl cysteine. In conclusion, the results demonstrate that metavanadate can inhibit cell proliferation via cell cycle arrest at G2/M phase in DU145 cells. Metavanadate-induced ROS formation may play an important role in this process by mediating the degradation of Cdc25C.

Key words: Metavanadate, G2/M cell cycle arrest, Cdc25C, Reactive oxygen species

中图分类号: 

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 20871008 and J0830836).
*Corresponding author. Tel.: 86-10-82801539