RRC ID 45440
Author Miyamoto C, Maehata Y, Motohashi K, Ozawa S, Ikoma T, Hidaka K, Wada-Takahashi S, Takahashi SS, Yoshino F, Yoshida A, Kubota E, Hata R, Lee MC.
Title Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell carcinoma.
Journal Biomed Res
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.
Volume 35(6)
Pages 381-8
Published 2014-1-1
DOI 10.2220/biomedres.35.381
PMID 25743344
MeSH 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives* 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology Animals Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Chemokines, CXC / genetics* Female Gene Expression Regulation, Neoplastic / physiology* Head and Neck Neoplasms / genetics Head and Neck Neoplasms / metabolism Head and Neck Neoplasms / pathology* Humans Mice Mice, Inbred BALB C Neoplasms, Experimental / genetics Neoplasms, Experimental / pathology Protein Kinase Inhibitors / pharmacology* RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Squamous Cell Carcinoma of Head and Neck rho-Associated Kinases / antagonists & inhibitors*
IF 1.217
Times Cited 8
Human and Animal Cells