SIRT1 Is Reduced in Gastric Adenocarcinoma and Acts as a Potential Tumor Suppressor in Gastric Cancer

作者：Yongguo Zhang, Xiqiang Cai, Na Chai, Yong Gu, Song Zhang, Meiling Ding, Haichao Cao, Sumei Sha, Jipeng Yin, Mengbin Li, Kaichun Wu, Yongzhan Nie · 发表于：Gastrointestinal Tumors · 年份：2015 · DOI：10.1159/000441460 · 被引用次数：12 · 研究领域：Sirtuins and Resveratrol in Medicine、Autophagy in Disease and Therapy、Genomics, phytochemicals, and oxidative stress

Background: Silent mating type information regulation 2 homolog 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase that is involved in a variety of biological processes. Recent studies have implicated the involvement of SIRT1 in tumorigenesis, but its role remains controversial even in the same tumor type. Summary: In this study, SIRT1 expression was examined in gastric adenocarcinoma by immunohistochemistry and quantitative real-time polymerase chain reaction. Cell proliferation, cell cycle, cell apoptosis and xenograft assays were performed to elucidate the roles of SIRT1 in gastric cancer. We found that SIRT1 expression was reduced in gastric adenocarcinoma at both the protein and mRNA levels. Tissue microarray analysis revealed a positive correlation between SIRT1 and p53 expression in gastric adenocarcinoma. Inhibition of SIRT1 by EX-527 or by shRNA-mediated silencing increased cell proliferation in vitro and in vivo. SIRT1 inhibition accelerated the G1-S phase transition and reduced apoptosis by regulating key factors involved in cell cycle control and apoptosis. On the contrary, the ectopic expression of SIRT1 or the activation of SIRT1 by resveratrol was sufficient to suppress the growth of gastric cancer cells in vitro and in vivo. Key Message: In our study, the ectopic expression or activation of SIRT1 arrested cells at the G1 phase b...