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ID 34239
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Author
Teraishi, Fuminori
Watanabe, Takanori
Tango, Yasuhisa
Kawashima, Takeshi
Umeoka, Tatsuo
Nisizaki, Masahiko
Tanaka, Noriaki
Abstract
The EGF (epidermal growth factor) receptor-tyrosine kinase inhibitor ZD1839 (Gefitinib, 'Iressa') blocks the cell signaling pathways involved in cell proliferation, survival, and angiogenesis in various cancer cells. TNF-related death apoptosis inducing ligand (TRAIL) acts as an anticancer agent. We investigated the antitumor effects of ZD1839 alone or in combination with TRAIL against human esophageal squamous cell cancer (ESCC) lines. Although all ESCC cells expressed EGF receptor at a protein level, the effect of ZD1839 on cell growth did not correlate with the level of EGFR expression and phosphorylation of EGF receptor protein in ESCC lines. ZD1839 caused a dose-dependent growth arrest at G0–G1 phase associated with increased p27 expression. As TE8 cells are resistant to TRAIL, we tested whether ZD1839 combined with TRAIL induced apoptosis of TE8 cells via the inhibition of EGF receptor signaling by ZD1839. ZD1839 inhibited the phosphorylation of Akt, and enhanced TRAIL-induced apoptosis via activation of caspase-3 and caspase-9, and inactivation of Bcl-xL. Our results indicated that ZD1839 has anti-cancer properties against human esophageal cancer cells. ZD1839 also augmented the anti-cancer activity of TRAIL, even in TRAIL-resistant tumors. These results suggest that treatment with ZD1839 and TRAIL may have potential in the treatment of ESCC patients.
Keywords
epidermal growth factor receptor
ZD1839
akt
esophageal squamous cell cancer
tumor necrosis factor-related apoptosis inducing ligand
Note
Digital Object Identifer:10.1016/j.febslet.2005.06.031
Published with permission from the copyright holder. This is the author's copy, as published in FEBS Letters, August 2005, Volume 579, Issue 19, Pages 4069-4075.
Publisher URL:http://dx.doi.org/10.1016/j.febslet.2005.06.031
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Copyright © 2005 Federation of European Biochemical Societies Published by Elsevier B.V. All rights reserved.
Published Date
2005-08-01
Publication Title
FEBS Letters
Volume
volume579
Issue
issue19
Publisher
Elsevier B.V.
Start Page
4069
End Page
4075
ISSN
0014-5793
NCID
AA00642943
Content Type
Journal Article
language
英語
Copyright Holders
Federation of European Biochemical Societies. Published by Elsevier B.V.
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author
Refereed
True
DOI
PubMed ID
Web of Sience KeyUT
Submission Path
biochemistry/2