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The Selective Cyclooxygenase-2 Inhibitor Nimesulide Prevents Helicobacter pylori-Associated Gastric Cancer Development in a Mouse Model

Authors
 Ki Taek Nam  ;  Ki-Baik Hahm  ;  Dae-Yong Kim  ;  Ki-Hwa Yang  ;  Dong Deuk Jang  ;  Jin Seok Kang  ;  Young-Bae Kim  ;  Byeongwoo Ahn  ;  Sang-Uk Han  ;  Marie Yeo  ;  Sang-Yeon Oh 
Citation
 CLINICAL CANCER RESEARCH, Vol.10(23) : 8105-8113, 2004 
Journal Title
CLINICAL CANCER RESEARCH
ISSN
 1078-0432 
Issue Date
2004
MeSH
Animals ; Apoptosis/drug effects ; Blotting, Western ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/therapeutic use* ; Gastric Mucosa/microbiology ; Helicobacter Infections/complications* ; Helicobacter Infections/drug therapy ; Helicobacter Infections/pathology ; Helicobacter pylori/pathogenicity* ; In Situ Nick-End Labeling ; Male ; Methylnitrosourea/toxicity ; Mice ; Mice, Inbred C57BL ; Prostaglandin-Endoperoxide Synthases/chemistry* ; Prostaglandin-Endoperoxide Synthases/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Stomach Neoplasms/chemically induced ; Stomach Neoplasms/microbiology ; Stomach Neoplasms/prevention & control* ; Sulfonamides/therapeutic use* ; bcl-2-Associated X Protein
Abstract
PURPOSE:
Helicobacter pylori infection can lead to gastric cancer, and cyclooxygenase-2 (COX-2) is overexpressed in the stomach during H. pylori infection. Therefore, we investigated whether nonsteroidal anti-inflammatory drugs might protect against this form of cancer. Specifically, we examined the chemopreventive effect of the COX-2 inhibitor nimesulide on H. pylori-associated gastric carcinogenesis in mice.
EXPERIMENTAL DESIGN:
C57BL/6 mice were treated with the carcinogen N-methyl-N-nitrosourea (MNU) and/or H. pylori. To determine the effect of COX-2 inhibition, nimesulide was mixed with feed pellets and administered for the duration of the experiment. All of the mice were sacrificed 50 weeks after the start of the experiment. Histopathology, immunohistochemistry, and Western blotting for COX-2, Bax and Bcl-2 were performed in stomach tissues. In vitro experiments with the human gastric cancer cell line AGS were also performed to identify mechanisms underlying cancer chemoprevention by nimesulide.
RESULTS:
Gastric tumors developed in 68.8% of mice that were given both MNU and H. pylori, whereas less than 10% developed gastric tumors when given either MNU or H. pylori alone. These findings indicate that H. pylori promotes carcinogen-induced gastric tumorigenesis. In mice treated with both MNU and H. pylori, nimesulide administration substantially reduced H. pylori-associated gastric tumorigenesis, whereas substantial inductions of apoptosis were observed. In vitro studies demonstrated that nimesulide and H. pylori when combined acted synergistically to induce more apoptosis than either alone.
CONCLUSIONS:
Our data show that nimesulide prevents H. pylori-associated gastric carcinogenesis, and suggest that COX-2 may be a target for chemoprevention of gastric cancer.
Files in This Item:
T200404856.pdf Download
DOI
10.1158/1078-0432.CCR-04-0896
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Nam, Ki Taek(남기택)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/113013
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