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
Kaken ID
publons
researchmap
Naomoto, Yoshio
Kawasaki Med Univ, Dept Gen Surg
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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.
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キーワード | Focal adhesion kinase
TAE226
Peritoneal dissemination
Prolonged survival
Anti-proliferation
Colon cancer
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発行日 | 2012-07-13
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出版物タイトル |
Biochemical and Biophysical Research Communications
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巻 | 423巻
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号 | 4号
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出版者 | Academic Press Inc Elsevier Science
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開始ページ | 744
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終了ページ | 749
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ISSN | 0006-291X
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NCID | AA00564395
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1016/j.bbrc.2012.06.030
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言語 |
英語
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著作権者 | (C) 2012 Elsevier Inc. All rights reserved.
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |