このエントリーをはてなブックマークに追加
ID 53005
フルテキストURL
著者
Yasugi, Masayuki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Takigawa, Nagio Kawasaki Hosp, Kawasaki Med Sch, Dept Gen Internal Med 4
Ochi, Nobuaki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Ohashi, Kadoaki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Harada, Daijiro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Ninomiya, Takashi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Murakami, Toshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Honda, Yoshihiro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Ichihara, Eiki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Tanimoto, Mitsune Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Kiura, Katsuyuki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med Kaken ID
抄録
Everolimus is an orally administered mTOR inhibitor. The effect, and mechanism of action, of everolimus on lung cancers with an epidermal growth factor receptor (EGFR) mutation remain unclear. Four gefitinib-sensitive and -resistant cell lines were used in the present work. Growth inhibition was determined using the MTT assay. Transgenic mice carrying the EGFR L858R mutation were treated with everolimus (10 mg/kg/day), or vehicle alone, from 5 to 20 weeks of age, and were then sacrificed. To evaluate the efficacy of everolimus in prolonging survival, everolimus (10 mg/kg/day) or vehicle was administered from 5 weeks of age. The four cell lines were similarly sensitive to everolimus. Expression of phosphorylated (p) mTOR and pS6 were suppressed upon treatment with everolimus in vitro, whereas the pAKT level increased. The numbers of lung tumors with a long axis exceeding 1 mm in the everolimus-treated and control groups were 1.9 +/- 0.9 and 9.4 +/- 3.2 (t-test, p<0.001), respectively. pS6 was suppressed during everolimus treatment. Although apoptosis and autophagy were not induced in everolimus-treated EGFR transgenic mice, angiogenesis was suppressed. The median survival time in the everolimus-treated group (58.0 weeks) was significantly longer than that in the control group (31.2 weeks) (logrank test, p<0.001). These findings suggest that everolimus had an indirect effect on tumor formation by inhibiting angiogenesis and might be effective to treat lung tumors induced by an activating EGFR gene mutation.
キーワード
Non-small cell lung cancer
Adenocarcinoma
Everolimus
mTOR
EGFR
発行日
2014-08-15
出版物タイトル
Experimental Cell Research
326巻
2号
開始ページ
201
終了ページ
209
ISSN
0014-4827
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/52961
言語
English
著作権者
(c) 2014 Elsevier Inc. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Science KeyUT