基础医学与临床 ›› 2008, Vol. 28 ›› Issue (7): 723-728.

• 研究论文 • 上一篇    下一篇

Rab5在胰腺癌细胞BxPC3中对 Notch1活性的调节

张娟 余和芬 张玉祥 王泽生   

  1. 首都医科大学生物化学与分子生物学 首都医科大学生物化学与分子生物学系 首都医科大学生物化学与分子生物学系 首都医科大学生物化学与分子生物学系
  • 收稿日期:2008-03-11 修回日期:2008-05-14 出版日期:2008-07-25 发布日期:2008-07-25
  • 通讯作者: 张玉祥

Regulation of Notch1 activity by Rab5 in pancreatic cancer BxPC3 cells

Juan ZHANG, He-fen YU, Yu-xiang ZHANG, Zhe-sheng WANG   

  1. Capital Medical University
  • Received:2008-03-11 Revised:2008-05-14 Online:2008-07-25 Published:2008-07-25
  • Contact: Yu-xiang ZHANG,

摘要: 目的 Notch在胰腺癌细胞中的生长中起着关键的调节作用,但是Notch活化的分子机制尚有未明之处。本研究主要集中于阐明内吞调节蛋白Rab5在Notch活化中的作用。 方法 用RNA干扰的方法抑制BxPC3细胞中Rab5蛋白的表达,用Western blot测定Notch1的活性型Notch ICD的表达的变化。磷脂酰肌醇-3-激酶(PI3激酶)被认为在内吞过程中起着非常关键的作用,我们分别用Wortmannin和LY294002抑制PI3激酶的活性,观察Notch活性的变化。 结果 抑制Rab5蛋白的表达,或者抑制PI3激酶的活性后,Notch1的活性型Notch ICD的表达量均显著下降,同时BxPC3细胞的生长受到抑制。结论 在胰腺癌细胞BxPC3中内吞调节蛋白质Rab5和PI3激酶在Notch活化中起着关键的作用,提示Notch的活化依赖于内吞。

关键词: 胰腺癌, BxPC3, Notch1, Rab5, Wortmannin, LY294002

Abstract: Objective To investigate the effect of Notch1 and Rab5 on the growth of pancreatic cancer BxPC3 cells and the regulation of Notch1 activity by Rab5 in BxPC3 cells. To investigate the effect of Wortmannin and LY294002 on the growth of pancreatic cancer BxPC3 cells and the regulation of Notch1 activity. Methods Notch1 and Rab5 expression were inhibited by siRNA interference. The growth rate of BxPC3 cells was measured by MTT. Rab5 expression was inhibited by siRNA interference ,the changes of Rab5 and Notch1 protein were measured by Western blot . Results The growth rate of BxPC3 cells decreased after inhibiting Notch1 and Rab5 expression. Notch1 protein level decreased after inhibiting Rab5 expression. After adding Wortmannin and LY294002, the growth of BxPC3 cells and Notch1 protein level decreased . Conclusion  In BxPC3 cells, Notch1 and Rab5 are important to cell growth. Rab5 may regulate Notch1 activity. Wortmannin and LY294002 are important to cell growth and regulate Notch1 activity.

Key words: pancreatic cancer, BxPC3, Notch1, Rab5, Wortmannin, LY294002