[The regulation of EKI-785 to the growth of U937 cell line]

Zhonghua Zhong Liu Za Zhi. 2006 Nov;28(11):810-4.
[Article in Chinese]

Abstract

Objective: The aim of this study was to explore the expression of erbBs in U937, an acute monocyte leukemia cell line, and their impact on the growth of this cell line.

Methods: Expression of erbBs was detected by RT-PCR and expression of erbB2 at protein level by Western blot. After U937 cells was treated with EKI-785, an irreversible specific inhibitor of erbBs, the growth was assessed by MTT and growth curve, apoptosis was detected by Annexin V-FITC Apoptosis Detection Kit, and signal pathway was detected by Western blot.

Results: erbB2-4 were expressed in U937 cell line, but not erbB1. Especially, protein of erbB2 was expressed in this cell line. After treating with EKI-785, the growth of U937 cells was inhibited and early apoptosis was induced. Moreover, the Ras/MAPK and the PI3K/Akt signaling pathways were all blocked.

Conclusion: erbBs may play key roles in the development of some leukemia. Therefore, erbBs may become new targets of treatment to leukemia, and EKI-785 has a potency of clinic use to leukemia.

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Proliferation / drug effects*
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quinazolines / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-4
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • U937 Cells

Substances

  • Quinazolines
  • RNA, Messenger
  • CL 387785
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-4
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase Kinases