Decitabine Inhibits Tumor Cell Proliferation and Up-Regulates E-Cadherin Expression in Epstein-Barr Virus-Associated Gastric Cancer
Decitabine Inhibits Tumor Cell Proliferation and Up-Regulates E-Cadherin Expression in Epstein-Barr Virus-Associated Gastric Cancer
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DOI：
10.1002/jmv.24634
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发表时间：
2017-03-01
影响因子：
12.7
通讯作者：
Sakaida, Isao
中科院分区：
文献类型：
--
作者：
Nakamura, Munetaka;Nishikawa, Jun;Sakaida, Isao
本研究探讨了DNA去甲基化药物地西他滨对EB病毒相关性胃癌(EBVaGC)的作用。地西他滨抑制EBVaGC细胞生长，诱导细胞发生G2/M期停滞和凋亡。在地西他滨作用下，E-钙粘附素表达上调，细胞运动受到明显抑制。P73和RUNX3启动子区域去甲基化，地西他滨上调其表达。它们增强p21的转录，通过下调c-Myc诱导G2/M期停滞和细胞凋亡。地西他滨还可诱导SNU719细胞BZLF1的表达。诱导EBV裂解感染是引起宿主细胞凋亡的另一种途径。这项研究首次揭示了去甲基化药物在EBVaGC中抑制肿瘤细胞增殖和上调E-钙粘蛋白的有效性。(C)2016威利期刊公司。
The present study investigated the effect of a DNA demethylating agent, decitabine, against Epstein-Barr virus-associated gastric cancer (EBVaGC). Decitabine inhibited cell growth and induced G2/M arrest and apoptosis in EBVaGC cell lines. The expression of E-cadherin was up-regulated and cell motility was significantly inhibited in the cells treated with decitabine. The promoter regions of p73 and RUNX3 were demethylated, and their expression was upregulated by decitabine. They enhanced the transcription of p21, which induced G2/M arrest and apoptosis through down-regulation of c-Myc. Decitabine also induced the expression of BZLF1 in SNU719. Induction of EBV lytic infection was an alternative way to cause apoptosis of the host cells. This study is the first report to reveal the effectiveness of a demethylating agent in inhibiting tumor cell proliferation and up-regulation of E-cadherin in EBVaGC. (C) 2016 Wiley Periodicals, Inc.