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- Title
Induction of cell cycle arrest and apoptosis in human nasopharyngeal carcinoma cells by ZD6474, an inhibitor of VEGFR tyrosine kinase with additional activity against EGFR tyrosine kinase.
- Authors
Xiao, Xia; Wu, Jiangxue; Zhu, Xiaofeng; Zhao, Peng; Zhou, Jinlin; Liu, Quentin Qiang; Zheng, Limin; Zeng, Musheng; Liu, Ranyi; Huang, Wenlin
- Abstract
ZD6474 is a vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The present study was undertaken to investigate the direct antiproliferative effect of ZD6474 on human nasopharyngeal carcinoma (NPC) in vitro and the antitumor activity on NPC xenografts in vivo. Results indicated that ZD6474 treatment inhibited EGFR phosphorylation and led to a dose- and time-dependent decrease in NPC cell (CNE-1, CNE-2 and C666-1) proliferation. Further investigation demonstrated G0/G1 cell cycle arrest in all 3 cell lines, which was associated with an upregulation of p21 and/or p27, and downregulation of CDK4, CDK6 and CDK2. ZD6474 treatment also induced apoptosis in CNE-1 and CNE-2 cells. The apoptosis mechanisms involved reduction of Bcl-2 and/or Bcl-X
- Publication
International Journal of Cancer, 2007, Vol 121, Issue 9, p2095
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.22955