Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell carcinoma
Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell carcinoma
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DOI：
10.2220/biomedres.35.381
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发表时间：
2014-12-01
影响因子：
1.2
通讯作者：
Lee, Masaichi-Chang-il
中科院分区：
文献类型：
--
作者：
Miyamoto, Chihiro;Maehata, Yojiro;Lee, Masaichi-Chang-il
CXCL14/BRAK （BRAK）是一种具有抗肿瘤活性的分泌性趋化因子，其在肿瘤细胞中的表达受到抑制。我们之前报道了BRAK在头颈部鳞状细胞癌（HNSCC）细胞系中的抗肿瘤活性以及抑制这些细胞中BRAK的分泌。法舒地尔是一种rho激酶（ROCK）抑制剂，可恢复纤维肉瘤细胞中的BRAK分泌。本研究通过检测BRAK在HNSCC细胞系中的基因表达和蛋白分泌来检测其抗肿瘤作用。我们发现BRAK介导法舒地尔对HNSCC细胞的抑制作用。法舒地尔抑制BALB/cAJcl-nu/nu雌性小鼠的肿瘤发展。法舒地尔还能显著刺激体外肿瘤细胞系分泌BRAK蛋白。同样，在培养的肿瘤细胞中加入法舒地尔后，BRAK蛋白的产生也显著增加。此外，法舒地尔在HNSCC细胞系中显著增加BRAK基因mRNA水平的表达。sirna抑制RhoA/ROCK通路显著刺激BRAK基因表达。这些结果表明，法舒地尔的肿瘤抑制作用是由BRAK介导的，这表明法舒地尔可能因此对治疗HNSCC有用。
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/cAJcl-nu/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.