Decitabine inhibits tumor cell proliferation and up-regulates e-cadherin expression in Epstein-Barr virus-associated gastric cancer

  • J Med Virol. 2017 Mar;89(3):508-517. doi: 10.1002/jmv.24634.
Munetaka Nakamura  1 ,  Jun Nishikawa  2 ,  Mari Saito  1 ,  Kouhei Sakai  3 ,  Sho Sasaki  1 ,  Shinichi Hashimoto  1 ,  Takeshi Okamoto  1 ,  Yutaka Suehiro  3 ,  Takahiro Yamasaki  3 ,  Isao Sakaida  1
Affiliations
  • 1. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
  • 2. Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
  • 3. Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
PMID: 27430892 DOI: 10.1002/jmv.24634
Abstract

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.

Keywords
Epstein-Barr virus; apoptosis/cell death; gastrointestinal analysis; tumor suppressor genes.
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