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.
| Original language | English (US) |
|---|---|
| Article number | 101319 |
| Journal | Redox Biology |
| Volume | 28 |
| DOIs | |
| State | Published - Jan 1 2020 |
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Keywords
- Antioxidant response
- Apoptosis
- Infection
- NF-κB
- Oxidative DNA damage
ASJC Scopus subject areas
- Biochemistry
- Organic Chemistry
Cite this
PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer. / Wang, Sen; Chen, Zheng; Zhu, Shoumin; Lu, Heng; Peng, Dunfa; Soutto, Mohammed; Naz, Huma; Peek, Richard; Xu, Hao; Zaika, Alexander; Xu, Zekuan; El-Rifai, Wael.
In: Redox Biology, Vol. 28, 101319, 01.01.2020.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer
AU - Wang, Sen
AU - Chen, Zheng
AU - Zhu, Shoumin
AU - Lu, Heng
AU - Peng, Dunfa
AU - Soutto, Mohammed
AU - Naz, Huma
AU - Peek, Richard
AU - Xu, Hao
AU - Zaika, Alexander
AU - Xu, Zekuan
AU - El-Rifai, Wael
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Antioxidant response
KW - Apoptosis
KW - Infection
KW - NF-κB
KW - Oxidative DNA damage
UR - http://www.scopus.com/inward/record.url?scp=85072179179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072179179&partnerID=8YFLogxK
U2 - 10.1016/j.redox.2019.101319
DO - 10.1016/j.redox.2019.101319
M3 - Article
C2 - 31536951
AN - SCOPUS:85072179179
VL - 28
JO - Redox Biology
JF - Redox Biology
SN - 2213-2317
M1 - 101319
ER -