Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells.
Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells.
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DOI：
10.5483/bmbrep.2009.42.10.655
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发表时间：
2009-10
期刊：
影响因子：
3.8
通讯作者：
S. O. Kim;B. Choi;I. Choi;J. Cheong;Gi-Young Kim;T. Kwon;N. Kim;Yung-Hyun Choi
中科院分区：
文献类型：
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作者：
S. O. Kim;B. Choi;I. Choi;J. Cheong;Gi-Young Kim;T. Kwon;N. Kim;Yung-Hyun Choi
采用组蛋白去乙酰化酶（HDAC）抑制剂，研究早期生长反应基因1（Egr-1）和紧密连接蛋白claudin-3在人肝癌细胞中的抗转移和抗侵袭作用。伤口愈合和Transwell实验结果表明，HDAC抑制剂如阿司他丁A和丁酸钠抑制细胞的迁移和侵袭。HDAC抑制剂在早期显著诱导Egr-1表达，之后表达水平下降。此外，在HDAC处理的细胞中，snail和1型胰岛素样生长因子受体（IGF-1 R）的下调诱导了血小板反应蛋白-1（TSP-1）、E-钙粘蛋白和claudin-3的上调。用Egr-1和claudin-3 siRNA转染的细胞显示出对HDAC介导的抗侵袭活性的显著阻断。总的来说，这些发现表明Egr-1和claudin-3的上调是HDAC介导的抗转移和抗侵袭的关键步骤。
The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor-treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.