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ID 50726
フルテキストURL
著者
Ueno, Tsuyoshi Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Tsukuda, Kazunori Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Toyooka, Shinichi Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Ando, Midori Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Takaoka, Munenori Kawasaki Med Univ, Dept Gen Surg
Soh, Junichi Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Asano, Hiroaki Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Maki, Yuho Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Muraoka, Takayuki Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Tanaka, Norimitsu Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Shien, Kazuhiko Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Furukawa, Masashi Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Yamatsuji, Tomoki Kawasaki Med Univ, Dept Gen Surg
Kiura, Katsuyuki Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Naomoto, Yoshio Kawasaki Med Univ, Dept Gen Surg
Miyoshi, Shinichiro Okayama Univ, Dept Gen Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
抄録
The anti-tumor activity of a newly developed Hsp90 inhibitor, NVP-AUY922 (AUY922), against non-small cell lung cancer (NSCLC) was examined. Twenty-one NSCLC cell lines were used, the somatic alterations of which were characterized. Cell proliferation was analyzed using a modified MTS assay. Expression of the client proteins was assessed using Western blotting. The cell cycle was analyzed using flow cytometry. The IC50 value of AUY922 for the NSCLC cell lines ranged from 5.2 to 860 nM (median, 20.4 nM). Based on previous data, cells with an IC50 of less than 50 nM were classified as sensitive cells and 19 of the 21 NSCLC cell lines were judged to be sensitive. The IC50 of five malignant pleural mesothelioma (MPM) cell lines revealed that the MPM cells had a significantly higher IC50 value (median, 89.2 nM; range, 22.2-24, 100 nM) than the NSCLC cells (p = 0.015). There was significant depletion of both the total and phosphorylated client proteins - EGFR, MET, HERZ and ART - at low drug concentrations (50-100 nM) in drug-sensitive cell lines. Cell-cycle analysis was performed for two sensitive cell lines, H1975 and H838. Following AUY922 treatment, an increase in the sub-G(0)-G(1) cell population, as well as appearance of cleaved PARP expression, indicated the induction of apoptosis. In conclusion, AUY922 was effective against most NSCLC cell lines, independent of the type of known molecular alteration, and appears to be a promising new drug for the treatment of NSCLC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
キーワード
NSCLC
Hsp90
AUY922
EGFR
EGFR-TKI
Mesothelioma
発行日
2012-04
出版物タイトル
Lung Cancer
76巻
1号
出版者
Elsevier Ireland Ltd.
開始ページ
26
終了ページ
31
ISSN
0169-5002
NCID
AA10785743
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1016/j.lungcan.2011.09.011
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/50671
言語
English
OAI-PMH Set
岡山大学
著作権者
(C) 2011 Elsevier Ireland Ltd. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT