MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells
MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells
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MCM-2 是曲古抑菌素 A 在结肠癌细胞中的治疗靶点
DOI：
10.1016/j.toxlet.2013.05.643
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发表时间：
2013-07-31
影响因子：
3.5
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
--
作者：
Liu, Yangbo;He, Gang;Zhang, Bo
组蛋白去乙酰化酶（HDAC）抑制剂是近年来出现的一类新型抗癌药物。曲古抑菌素A（TSA）是一种经典的HDAC抑制剂，已被证明可诱导细胞周期阻滞，促进细胞凋亡，并抑制转移。然而，TSA功能的分子机制尚未完全阐明。在本研究中，我们通过RT-PCR阵列发现TSA处理诱导HCT 116细胞中细胞周期相关基因的表达改变。在84个与细胞周期调控相关的基因中，TSA处理后有34个基因发生显著改变，其中7个基因表达上调，27个基因表达下调。有趣的是，TSA处理显着下调了微小染色体维持蛋白-2（MCM-2）的基因表达。通过定量RT-PCR和Western印迹证实了这一点。此外，MCM-2的siRNA沉默导致HCT 116细胞的细胞周期停滞和凋亡。此外，TSA引起磷酸化JNK的增加，这参与了MCM-2的下调。总之，我们的结果表明MCM-2是TSA在结肠癌细胞中的一个新的治疗靶点。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Histone deacetylase (HDAC) inhibitors have recently emerged as a new class of anti-cancer agents. Trichostatin A (TSA), a classical HDAC inhibitor, has been demonstrated to induce cell cycle arrest, promote cell apoptosis, and inhibit metastasis. However, the molecular mechanism underlying TSA function has not been fully elucidated. In the current study, we found that TSA treatment induced altered expression of cell cycle-associated genes in HCT116 cells by RT-PCR array. Among the 84 genes related to cell cycle control, 34 genes were significantly altered by TSA treatment, with 7 genes upregulated and 27 genes downregulated. Interestingly, gene expression of minichromosome maintenance protein-2 (MCM-2) was significantly downregulated by TSA treatment. This was confirmed by quantitative RT-PCR and Western blotting. Moreover, silencing of MCM-2 by siRNA led to cell cycle arrest and apoptosis in HCT116 cells. In addition, TSA caused an increase of phosphorylated JNK, which was involved in downregulation of MCM-2. Together, our results suggest that MCM-2 is a noval therapeutic target of TSA in colon cancer cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.