Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell carcinoma

Chihiro MIYAMOTO; Yojiro MAEHATA; Kazuhiko MOTOHASHI; Shigeyuki OZAWA; Takeharu IKOMA; Kouki HIDAKA; Satoko WADA-TAKAHASHI; Shun-Suke TAKAHASHI; Fumihiko YOSHINO; Ayaka YOSHIDA; Eiro KUBOTA; Ryu-Ichiro HATA; Masaichi-Chang-il LEE

doi:10.2220/biomedres.35.381

Full Papers

Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell carcinoma

Chihiro MIYAMOTO, Yojiro MAEHATA, Kazuhiko MOTOHASHI, Shigeyuki OZAWA, Takeharu IKOMA, Kouki HIDAKA, Satoko WADA-TAKAHASHI, Shun-Suke TAKAHASHI, Fumihiko YOSHINO, Ayaka YOSHIDA, Eiro KUBOTA, Ryu-Ichiro HATA, Masaichi-Chang-il LEE

Author information

Chihiro MIYAMOTO
Department of Oral Science, Graduate School, Kanagawa Dental University
Oral Health Science Research Center, Graduate School, Kanagawa Dental University
Yojiro MAEHATA
Department of Oral Science, Graduate School, Kanagawa Dental University
Oral Health Science Research Center, Graduate School, Kanagawa Dental University
Kazuhiko MOTOHASHI
Department of Oral Science, Graduate School, Kanagawa Dental University
Shigeyuki OZAWA
Oral Health Science Research Center, Graduate School, Kanagawa Dental University
Department of Oral Surgery, Graduate School, Kanagawa Dental University
Takeharu IKOMA
Oral Health Science Research Center, Graduate School, Kanagawa Dental University
Department of Oral Surgery, Graduate School, Kanagawa Dental University
Kouki HIDAKA
Department of Periodontal Regeneration, Kanagawa Dental University
Satoko WADA-TAKAHASHI
Department of Oral Science, Graduate School, Kanagawa Dental University
Shun-Suke TAKAHASHI
Department of Oral Science, Graduate School, Kanagawa Dental University
Fumihiko YOSHINO
Department of Oral Science, Graduate School, Kanagawa Dental University
Ayaka YOSHIDA
Department of Oral Science, Graduate School, Kanagawa Dental University
Eiro KUBOTA
Oral Health Science Research Center, Graduate School, Kanagawa Dental University
Department of Oral Surgery, Graduate School, Kanagawa Dental University
Ryu-Ichiro HATA
Department of Oral Science, Graduate School, Kanagawa Dental University
Oral Health Science Research Center, Graduate School, Kanagawa Dental University
Masaichi-Chang-il LEE
Yokosuka-Shonan Disaster Health Emergency Research Center, Graduate School, Kanagawa Dental University

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2014 Volume 35 Issue 6 Pages 381-388

DOI https://doi.org/10.2220/biomedres.35.381

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Abstract

CXCL14/BRAK (BRAK) is a secreted chemokine with anti-tumor activity, and its expression is suppressed in tumor cells. We previously reported the anti-tumor activity of BRAK in cell lines of head and neck squamous cell carcinoma (HNSCC) and the suppression of BRAK secretion in these cells. BRAK secretion in fibrosarcoma cells is restored by Fasudil, which is a Rho-kinase (ROCK) inhibitor. In this study, we examined the anti-tumor effect of BRAK by evaluating its gene expression and protein secretion in HNSCC cell lines. We found that BRAK mediated the suppressive effect of Fasudil against HNSCC cells. Tumor development in female BALB/cAJclnu/nu mice was suppressed by Fasudil. Also secretion of BRAK protein by tumor cell lines in vitro was significantly stimulated by Fasudil treatment. Similarly, the production of BRAK protein was significantly increased by the addition of Fasudil to cultured tumor cells. Furthermore Fasudil significantly increased BRAK gene expression at the mRNA level in HNSCC cell line. Inhibition of the RhoA/ROCK pathway by siRNAs significantly stimulated BRAK gene expression. These results show that the tumor-suppressive effect of Fasudil was mediated by BRAK, suggesting that Fasudil may therefore be useful for the treatment of HNSCC.

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