Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
J Med Virol. 2017 Mar;89(3):508-517. doi: 10.1002/jmv.24634. Epub 2016 Nov 17.
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 up-regulated 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. J. Med. Virol. 89:508-517, 2017. © 2016 Wiley Periodicals, Inc.
本研究调查了去甲基化剂地西他滨对 Epstein-Barr 病毒相关胃癌（EBVaGC）的作用。地西他滨抑制 EBVaGC 细胞系的细胞生长，并诱导 G2/M 期阻滞和细胞凋亡。用地西他滨处理的细胞中 E-钙黏蛋白的表达上调，细胞迁移明显受到抑制。p73 和 RUNX3 的启动子区域被去甲基化，地西他滨上调其表达。它们通过下调 c-Myc 增强了 p21 的转录，从而通过下调 c-Myc 诱导 G2/M 期阻滞和细胞凋亡。地西他滨还诱导 SNU719 中 BZLF1 的表达。诱导 EBV 裂解感染是导致宿主细胞凋亡的另一种方式。本研究首次报道了去甲基化剂抑制肿瘤细胞增殖和上调 EBVaGC 中 E-钙黏蛋白的有效性。医学病毒杂志 89:508-517, 2017。© 2016 Wiley Periodicals, Inc.
