Molecular and Cellular Biochemistry

, Volume 340, Issue 1–2, pp 107–114

Cbl-b promotes chemotherapy-induced apoptosis in rat basophilic leukemia cells by suppressing PI3K/Akt activation and enhancing MEK/ERK activation

  • Xiujuan Qu
  • Yingchun Li
  • Jing Liu
  • Ling Xu
  • Ye Zhang
  • Xuejun Hu
  • Kezuo Hou
  • Yunpeng Liu
Article

Abstract

The ubiquitin ligase Cbl-b is a negative regulator of the PI3K/Akt pathway, the survival pathway implicated in chemotherapy resistance. However, it remains unclear whether Cbl-b can regulate chemosensitivity through modulating Akt activation. In this study, VP-16-induced RBL-2H3 cells apoptosis was accompanied by the activation of Akt and ERK. The PI3K inhibitor LY294002, not the ERK inhibitor PD98059, enhanced the apoptosis. In addition, down-regulation of Cbl-b was also detected. Over expression of Cbl-b significantly enhanced VP-16-induced cell apoptosis with inhibition of Akt activity, while a dominant negative (DN) RING Finger domain mutation completely abolished this enhancement. On the other hand, ERK activity was enhanced by Cbl-b, and the ERK inhibitor PD98059 reversed Cbl-b-enhanced apoptosis. The consistent results were also showed in the process of Ara-c treatment. These observations indicate that Cbl-b promotes RBL-2H3 apoptosis induced by VP-16 or Ara-c, probably through inhibition of Akt and activation of ERK.

Keywords

Cbl-b Chemosensitivity PI3K/Akt pathway ERK pathway 

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Xiujuan Qu
    • 1
  • Yingchun Li
    • 1
  • Jing Liu
    • 1
  • Ling Xu
    • 1
  • Ye Zhang
    • 1
  • Xuejun Hu
    • 2
  • Kezuo Hou
    • 1
  • Yunpeng Liu
    • 1
  1. 1.Department of Medical OncologyThe First Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Respiratory MedicineThe First Hospital of China Medical UniversityShenyangChina

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