Fasudil Suppresses Fibrosarcoma Growth by Stimulating Secretion of the Chemokine CXCL14/BRAK

• Miyamoto Chihiro

  Department of Clinical Care Medicine, Division of Pharmacology and ESR Laboratories, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

• Maehata Yojiro

  Department of Clinical Care Medicine, Division of Pharmacology and ESR Laboratories, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

• Ozawa Shigeyuki

  Department of Oral Surgery, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

• Ikoma Takeharu

  Department of Oral Surgery, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

• Kubota Eiro

  Department of Oral Surgery, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

• Izukuri Kazuhito

  Department of Biochemistry and Molecular Biology, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

• Kato Yasumasa

  Department of Oral Function & Molecular Biology, Ohu University School of Dentistry, Japan

• Hata Ryu-Ichiro

  Department of Biochemistry and Molecular Biology, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

• Lee Masaichi-Chang-il

  Department of Oral Surgery, Kanagawa Dental College, Japan Oral Health Science Research Center, Kanagawa Dental College, Japan

抄録

We previously reported that chemokine CXCL14/BRAK (BRAK) has antitumor activity in several carcinoma cells indicating that BRAK secretion suppresses carcinoma cells. Ras-homologous small GTPase (RhoA) and Rho-associated coiled-coil-containing protein kinase (ROCK) are important regulators of secretory processes, and activation of the RhoA/ROCK signaling pathway stimulates tumor invasion and metastasis. We investigated the effects of fasudil, a specific ROCK inhibitor, on BRAK secretion and tumor progression in mesenchymal fibrosarcoma cells (MC57). We demonstrated the antitumor activity of secreted BRAK using MC57 transplantation of BRAK in overexpressed transgenic mice. Further, to eliminate the influence of change in the mRNA expression of endogenous BRAK, we produced stable MC57 cell lines expressing BRAK (MC57-BRAK) or mock vector (MC57-MOCK). Fasudil significantly increased BRAK secretion by MC57-BRAK cells in a dose-dependent manner. To determine the effect of fasudil on tumor growth, MC57-BRAK and MC57-MOCK cells were transplanted into wild-type mice. Fasudil treatment suppressed tumor growth only in mice that had received MC57-BRAK cell transplants. These results indicate that fasudil inhibits fibrosarcoma growth by stimulating BRAK secretion and suggests that fasudil therapy might have clinical efficacy.

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 120 (3), 241-249, 2012

  公益社団法人 日本薬理学会

キーワード

• Ras-homologous small GTPase
• fasudil
• 5-(1,4-diazepane-1-sulfonyl) isoquinoline
• fibrosarcoma cell
• CXCL14/BRAK

詳細情報

• CRID: 1390282680155740032
• NII論文ID: 10031147570
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.12177fp
• COI: 1:STN:280:DC%2BC3s%2Fot1eksg%3D%3D
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 024093874
• PubMed: 23099322
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I024093874
• Web Site: https://search.jamas.or.jp/link/ui/2013228291
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可