The selective cyclooxygenase-2 inhibitor nimesulide prevents Helicobacter pylori-associated gastric cancer development in a mouse model

Ki Taek Nam, Ki Baik Hahm, Sang Yeon Oh, Marie Yeo, Sang Uk Han, Byeongwoo Ahn, Young Bae Kim, Jin Seok Kang, Dong Deuk Jang, Ki Hwa Yang, Dae Yong Kim

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8105-8113
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number23
DOIs
Publication statusPublished - 2004 Dec 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The selective cyclooxygenase-2 inhibitor nimesulide prevents Helicobacter pylori-associated gastric cancer development in a mouse model'. Together they form a unique fingerprint.

  • Cite this

    Nam, K. T., Hahm, K. B., Oh, S. Y., Yeo, M., Han, S. U., Ahn, B., Kim, Y. B., Kang, J. S., Jang, D. D., Yang, K. H., & Kim, D. Y. (2004). The selective cyclooxygenase-2 inhibitor nimesulide prevents Helicobacter pylori-associated gastric cancer development in a mouse model. Clinical Cancer Research, 10(23), 8105-8113. https://doi.org/10.1158/1078-0432.CCR-04-0896