Orignal Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 14, 2009; 15(22): 2731-2738
Published online Jun 14, 2009. doi: 10.3748/wjg.15.2731
Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions
Li-Jing Zhang, Shi-Yan Wang, Xiao-Hui Huo, Zhen-Long Zhu, Jian-Kun Chu, Jin-Cheng Ma, Dong-Sheng Cui, Ping Gu, Zeng-Ren Zhao, Ming-Wei Wang, Jun Yu
Li-Jing Zhang, Xiao-Hui Huo, Jian-Kun Chu, Jin-Cheng Ma, Jun Yu, Department of Gastroenterology, the First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China
Shi-Yan Wang, Jun Yu, Department of Medicine and Therapeutics, the Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, China
Zhen-Long Zhu, Department of Pathology, the First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China
Dong-Sheng Cui, Ping Gu, Ming-Wei Wang, Department of Neurology, the First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China
Zeng-Ren Zhao, Department of Surgery, the First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China
Author contributions: Zhang LJ and Wang SY contributed equally to this work; Yu J, Ma JC and Wang MW designed the research; Zhang LJ, Huo XH, Zhu ZL, Chu JK, Ma JC, Cui DS, Gu P, Zhao ZR and Yu J performed the research; Zhang LJ, Wang SY and Yu J analyzed the data; Zhang LJ, Wang SY and Yu J wrote the paper.
Correspondence to: Jun Yu, MD, PhD, Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. junyu@cuhk.edu.hk
Telephone: +852-26321195
Fax: +852-26321194
Received: March 8, 2009
Revised: April 14, 2009
Accepted: April 21, 2009
Published online: June 14, 2009
Abstract

AIM: To evaluate whether celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, could reduce the severity of gastric precancerous lesions following Helicobacter pylori (H pylori) eradication.

METHODS: H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib (n = 30) or placebo (n = 30) for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E2 (PGE2) assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density (MVD) assay using CD31 staining.

RESULTS: COX-2 protein expression was significantly increased in gastric precancerous lesions (atrophy, intestinal metaplasia and dysplasia, respectively) compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo (P < 0.001). Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib (P = 0.002) compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression (P < 0.001) and COX-2 activity (P < 0.001) in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation (P < 0.01), induced cell apoptosis (P < 0.01) and inhibited angiogenesis with decreased MVD (P < 0.001). However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARγ expression, a protective molecule with anti-neoplastic effects.

CONCLUSION: H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.

Keywords: Apoptosis; Cyclooxygenase 2; Gastric precancerous lesions; Helicobacter pylori; Microvessel density; Proliferation