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ID 52022
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Author
Takeda, Hiromasa
Takigawa, Nagio
Ohashi, Kadoaki
Minami, Daisuke
Kataoka, Itaru
Ichihara, Eiki
Ochi, Nobuaki
Kiura, Katsuyuki Kakenhi
Abstract
The effectiveness of vandetanib, an agent that targets RET, VEGFR and EGFR signaling, against EGFR-mutant lung cancer cells with PTEN loss was investigated. Two EGFR mutant non-small cell lung cancer (NSCLC) cell lines, PC-9 (PTEN wild type) and NCI-H1650 (PTEN null), were used. We transfected an intact FTEN gene into H1650 cells and knocked down PTEN expression in PC-9 cells using shRNA. The effectiveness of gefitinib and vandetanib was assessed using a xenograft model. While PC-9 cells were more resistant to vandetanib than gefitinib, H1650 cells were more sensitive to vandetanib than gefitinib. Both gefitinib and vandetanib suppressed the activation of EGFR and MAPK in H1650 cells, although phosphorylated AKT levels were not affected. In an H1650 cell xenograft model, vandetanib was also more effective than gefitinib. Although PTEN-transfected H1650 cells did not show restoration of sensitivity to gefitinib in vitro, the xenograft tumors responded to gefitinib and vandetanib. Knockdown of PTEN in PC-9 cells caused resistance to gefitinib. In conclusion, vandetanib might be effective in NSCLC with EGFR mutations that lack FTEN expression. The contribution of PTEN absence to vandetanib activity in NSCLC cells harboring EGFR mutations should be further examined.
Keywords
Lung cancer
Vandetanib
Gefitinib
EGFR
VEGFR
PTEN
Published Date
2013-02-15
Publication Title
Experimental Cell Research
Volume
volume319
Issue
issue4
Start Page
417
End Page
423
ISSN
0014-4827
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1016/j.yexcr.2012.12.018
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/51953
language
英語
Copyright Holders
(C) 2012 Elsevier Inc. All rights reserved.
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Refereed
True
DOI
Web of Sience KeyUT