@article{e63347c8025441769a2788c257a6a478,
title = "PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer",
abstract = "Background: Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The role of antioxidant enzyme peroxiredoxin 2 (PRDX2) in gastric tumorigenesis remains unknown. In vitro (AGS and SNU-1 cell lines) and in vivo mouse models were utilized to investigate the role of PRDX2 in response to H. pylori infection (7.13, J166 or PMSS1 strain). We detected high levels of PRDX2 expression in gastric cancer tissues. Gastric cancer patients with high expression levels of PRDX2 had significantly worse overall and progression-free survival than those with low levels. H. pylori infection induced activation of NF-κB with increased expression of PRDX2, in in vitro and in vivo models. The knockdown of PRDX2 led to an increase in the levels of reactive oxygen species (ROS), oxidative DNA damage, and double-strand DNA breaks, in response to H. pylori infection, as measured by H2DCFDA, 8-oxoguanine, and p-H2AXγ assays. Luciferase reporter and ChIP assays confirmed the presence of a putative binding site of NF-κB-p65 on PRDX2 promoter region. The inhibition of PRDX2 significantly sensitized AGS and SNU-1 cells to cisplatin treatment. Our data suggest that the future development of therapeutic approaches targeting PRDX2 may be useful in the treatment of gastric cancer.",
keywords = "Antioxidant response, Apoptosis, Infection, NF-κB, Oxidative DNA damage",
author = "Sen Wang and Zheng Chen and Shoumin Zhu and Heng Lu and Dunfa Peng and Mohammed Soutto and Huma Naz and Richard Peek and Hao Xu and Alexander Zaika and Zekuan Xu and Wael El-Rifai",
note = "Funding Information: Research reported in this publication was supported by a Research Career Scientist award (1IK6BX003787) and merit award (I01BX001179) from the U.S. Department of Veterans Affairs (W. El-Rifai), and the following grants from the U.S. National Institutes of Health: R01CA93999 and Sylvester Comprehensive Cancer Center (P30CA240139). This work was partially supported by the National Natural Science Foundation of China (81572362); the National Natural Science Foundation Project of International Cooperation (NSFC-NIH, 81361120398); the Primary Research & Development Plan of Jiangsu Province (BE2016786). The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the Department of Veterans Affairs, National Institutes of Health, University of Miami, or Nanjing Medical University. Funding Information: Research reported in this publication was supported by a Research Career Scientist award ( 1IK6BX003787 ) and merit award ( I01BX001179 ) from the U.S. Department of Veterans Affairs (W. El-Rifai), and the following grants from the U.S. National Institutes of Health : R01CA93999 and Sylvester Comprehensive Cancer Center ( P30CA240139 ). This work was partially supported by the National Natural Science Foundation of China ( 81572362 ); the National Natural Science Foundation Project of International Cooperation ( NSFC-NIH, 81361120398 ); the Primary Research & Development Plan of Jiangsu Province ( BE2016786 ). The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the Department of Veterans Affairs, National Institutes of Health, University of Miami, or Nanjing Medical University. Publisher Copyright: {\textcopyright} 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2020",
month = jan,
doi = "10.1016/j.redox.2019.101319",
language = "English (US)",
volume = "28",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier BV",
}