Copyright
©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 21, 2009; 15(39): 4907-4914
Published online Oct 21, 2009. doi: 10.3748/wjg.15.4907
Short-term Celecoxib intervention is a safe and effective chemopreventive for gastric carcinogenesis based on a Mongolian gerbil model
Chao-Hung Kuo, Huang-Ming Hu, Pei-Yun Tsai, I-Chen Wu, Sheau-Fang Yang, Lin-Li Chang, Jaw-Yuan Wang, Chang-Ming Jan, Wen-Ming Wang, Deng-Chyang Wu
Chao-Hung Kuo, Huang-Ming Hu, Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 813, Taiwan, China
Chao-Hung Kuo, I-Chen Wu, Chang-Ming Jan, Wen-Ming Wang, Deng-Chyang Wu, Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, China
Chao-Hung Kuo, Jaw-Yuan Wang, Chang-Ming Jan, Wen-Ming Wang, Deng-Chyang Wu, Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, China
Pei-Yun Tsai, Department of Nursing, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 813, Taiwan, China
Sheau-Fang Yang, Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, China
Lin-Li Chang, Department of Microbiology, Kaohsiung Medical University, Kaohsiung 807, Taiwan, China
Jaw-Yuan Wang, Division of Gastrointestinal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, China
Author contributions: Kuo CH designed the study, collected and analyzed the data, supervised the collection, and wrote the manuscript; Hu HM, Tsai PY, Wu IC, Chang LL, Wang JY, Jan CM, Wang WM participated in the design and coordination of the work involved; Yang SF was the consultant overseeing the histopathological findings; Wu DC participated in the study design and coordination, and supervised the study; All authors have approved the final draft submitted.
Supported by A grant from Kaohsiung Medical University (Q096014), and Kaohsiung Municipal Hsiao-Kang Hospital (kmhk-96-005, kmhk-95-005). This study was approved by the Institutional Animal Care and Use Committee, Kaohsiung Medical University
Correspondence to: Deng-Chyang Wu, MD, PhD, Chief, Department of Gastroenterology, Kaohsiung Medical University Hospital, 100 Tz-You 1st Road, Kaohsiung City 807, Taiwan, China. dechwu@yahoo.com
Telephone: +886-7-3121101-7451 Fax: +886-7-3135612
Received: July 28, 2009
Revised: August 31, 2009
Accepted: September 6, 2009
Published online: October 21, 2009
AIM: To evaluate the optimal intervention point of a selective cyclooxygenase-2 (COX-2) inhibitor, Celecoxib, for inhibiting Helicobacter pylori (H pylori)-associated gastric carcinogenesis in Mongolian gerbils (MGs).
METHODS: One hundred and twelve MGs were divided into six groups (A-F). One hundred gerbils were inoculated with H pylori (groups A-E). Twelve gerbils were inoculated with vehicle broth only (group F). After 4 wk, they were given N’-methyl-N’-nitro-N-nitroso-guanidine (MNNG) (50 μg/mL) in the drinking water for 20 wk. In groups B-E, the animals were given the stock Celecoxib (10 mg/kg per day) diet from the 21st, 31st, 21st and 41st week respectively. The periods of administering Celecoxib were 30, 20, 20, and 15 wk respectively. On the 51st week, the animals were sacrificed for histological examination. Local PCNA expression was examined by the immunohistochemistry method. The expression of COX-2 protein was assessed by Western Blot. Analysis used the χ2 test. The difference was regarded as significant when P value was less than 0.05.
RESULTS: Seventeen percent (17/100) of H pylori-infected MGs developed gastric cancer. All of these lesions were well-differentiated adenocarcinoma. The incidence rates of adenocarcinoma in groups A-F were 40%, 0%, 0%, 20%, 25%, and 0% respectively. The inflammatory scores were higher in group B than in other groups. There was no inflammatory response noted in group F. Celecoxib treatment resulted in a significant reduction in the proliferation of H pylori-infected mucosal cells (groups B, C and D) (P < 0.01).The expression of COX-2 protein was significantly attenuated in the groups which were Celecoxib-treated for more than 20 wk (groups B, C, D). The groups treated with Celecoxib had a significantly lower rate of advanced gastric cancer (34% vs 75%, P < 0.001) There were no sudden deaths in any of the groups.
CONCLUSION: Short-term treatment with Celecoxib has an anti-carcinogenic effect, and resulted in less severe inflammation and inhibited the invasive degree of gastric cancer.
