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Digestion. 2010;81(3):193-203. doi: 10.1159/000252790. Epub 2010 Jan 19.

Celecoxib inhibits CD133-positive cell migration via reduction of CCR2 in Helicobacter pylori-infected Mongolian gerbils.

Author information

1
Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Tokyo, Japan. seiji.futagami@gmail.com

Abstract

BACKGROUND/AIMS:

To see whether celecoxib prevents gastric cancer occurrence by disrupting the progression of chronic gastritis into gastric carcinoma through its inhibition of the migration of CD133-positive cells, one of the surface markers of bone marrow-derived cells, in Helicobacter pylori-infected gerbils.

METHODS:

70 gerbils were divided into six groups. Group 1 gerbils served as control (n = 6). 10 gerbils were given N-methyl-N-nitrosourea (MNU), 30 ppm (group 2). 6 short-term Helicobacter pylori-infected gerbils (group 3) were sacrificed after 8 weeks of H. pylori infection and 6 long-term H. pylori-infected gerbils were sacrificed after 42 weeks of H. pylori infection (group 4). 20 gerbils were given MNU pretreatment and long-term H. pylori infection (group 5). In addition, after H. pylori inoculation, 22 gerbils also received a celecoxib in their diet (group 6). CD133 and CCR2 expression in gastric tissues was evaluated by Western blot analysis and immunostaining.

RESULTS:

CD133-positive cells were mainly localized in the bottom of the gastric epithelial cells. CD133-positive cells also migrated into gastric cancer tissues in this model. CD133-positive cells in MNU-pretreated H. pylori-infected gerbils were significantly increased compared to those in H. pylori short-term infected gerbils. Celecoxib treatment significantly reduced CD133-positive cell migration and CCR2 expression levels. CD133- and CCR2-positive cells were colocalized in H. pylori-infected gastritis and gastric cancer tissues. Celecoxib treatment significantly reduced the number of CD133- and CCR2-positive cells.

CONCLUSIONS:

Celecoxib inhibits CD133-positive cell migration via the reduction of CCR2 in this model. Further studies are needed to clarify the precise mechanisms driving H. pylori infection-induced CD133-positive cell migration and its link to the progression of chronic gastritis into gastric cancer.

PMID:
20090335
DOI:
10.1159/000252790
[Indexed for MEDLINE]
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