PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer
Year: 2019
Type: article
Abstract: 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.
Source: Redox Biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,850
Funders: U.S. Department of Veterans Affairs, University of Miami, Sylvester Comprehensive Cancer Center, University of Miami Health Systems, National Natural Science Foundation of China, Government of Jiangsu Province, Nanjing Medical University, National Institutes of Health, National Outstanding Youth Science Fund Project of National Natural Science Foundation of China, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: The role of NRF2 in reflux-induced esophageal adenocarcinomas, Targets of Gene Overexpression at 17q in Gastric Tumorigenesis: Darpp32, G1542872477, G1788479481, G1913464076, G2065299061, G2732270628, G3031895702, G305175183, G3203831490, G3618326370, Mechanisms of Tumorigenic Transformation of Barretts Esophagus, G702371463, G8168297746, G8616801171, G8710842620, G9000268584, Molecular and Cellular Basis for Digestive Diseases, H. Pylori Relationship to Digestive Diseases and Cancer, New carcinogenic mechanisms of Helicobacter pylori infection, H. pylori-induced Inflammation and Gastric Cancer, The Sylvester Cancer Center Support Grant, G920921055
OpenAlex ID: W2971379494