Anti-Helicobacterpylori therapy followed by celecoxib on progression of gastric precancerous lesions |
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Authors: | 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 |
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Affiliation: | 1. Department of Gastroenterology,the First Affiliated Hospital of Hebei Medical University,Shijiazhuang 050051,Hebei Province,China 2. Department of Medicine and Therapeutics,the Prince of Wales Hospital,the Chinese University of Hong Kong,Hong Kong,China 3. Department of Pathology,the First Affiliated Hospital of Hebei Medical University,Shijiazhuang 050051,Hebei Province,China 4. Department of Neurology,the First Affiliated Hospital of Hebei Medical University,Shijiazhuang 050051,Hebei Province,China 5. Department of Surgery,the First Affiliated Hospital of Hebei Medical University,Shijiazhuang 050051,Hebei Province,China 6. Department of Gastroenterology,the First Affiliated Hospital of Hebei Medical University,Shijiazhuang 050051,Hebei Province,China;Department of Medicine and Therapeutics,the Prince of Wales Hospital,the Chinese University of Hong Kong,Hong Kong,China |
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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 PPARg 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. |
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Keywords: | Apoptosis Cyclooxygenase 2 Gastric precancerous lesions Helicobacter pylori Microvessel density Proliferation |
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