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ID 49564
フルテキストURL
著者
Hao, Hui-fang Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Takaoka, Munenori Kawasaki Med Univ, Dept Gen Surg
Bao, Xiao-hong Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Wang, Zhi-gang Inner Mongolia Univ, Coll Life Sci, Key Lab Mammal Reprod Biol & Biotechnol, Minist Educ
Tomono, Yasuko Shigei Med Res Inst, Div Mol & Cell Biol
Sakurama, Kazufumi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Ohara, Toshiaki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Fukazawa, Takuya Kawasaki Med Univ, Dept Gen Surg
Yamatsuji, Tomoki Kawasaki Med Univ, Dept Gen Surg
Fujiwara, Toshiyoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol ORCID 科研費研究者番号
Naomoto, Yoshio Kawasaki Med Univ, Dept Gen Surg
抄録
Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken together, a possible strategy for inhibiting peritoneal dissemination by targeting FAK with TAE226 appears to be applicable through anti-proliferative and anti-invasion/anti-migration mechanisms.
キーワード
Focal adhesion kinase
TAE226
Peritoneal dissemination
Prolonged survival
Anti-proliferation
Colon cancer
発行日
2012-07-13
出版物タイトル
Biochemical and Biophysical Research Communications
423巻
4号
出版者
Academic Press Inc Elsevier Science
開始ページ
744
終了ページ
749
ISSN
0006-291X
NCID
AA00564395
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.bbrc.2012.06.030
言語
English
著作権者
(C) 2012 Elsevier Inc. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT