Gastric Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2005; 11(1): 41-45
Published online Jan 7, 2005. doi: 10.3748/wjg.v11.i1.41
Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: Implications on chemoprevention
Jun Yu, Bao-Dong Tang, Wai K. Leung, Ka-Fai To, Alfa H.C. Bai, Zhi-Rong Zeng, Po-Ki Ma, Minnie Y.Y. Go, Pin-Jin Hu, Joseph J.Y. Sung
Jun Yu, Wai K. Leung, Alfa H.C. Bai, Po-Ki Ma, Minnie Y.Y. Go, Joseph J.Y. Sung, Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Bao-Dong Tang, Zhi-Rong Zeng, Pin-Jin Hu, Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University of Medical Sciences, Guangzhou 510080, Guangdong Province, China
Ka-Fai To, Department of Anatomical & Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Author contributions: All authors contributed equally to the work.
Supported by an unrestricted grant From the Hong Kong Society of Digestive Endoscopy and the Natural Science Foundation of Guangdong Province of China (No. 010713)
Correspondence to: Dr. Wai K. Leung, Department of Medicine & Therapeutics, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China. wkleung@cuhk.edu.hk
Telephone: +852-26323140 Fax: +852-26373852
Received: April 24, 2004
Revised: April 28, 2004
Accepted: June 18, 2004
Published online: January 7, 2005
Abstract

AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group. This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism.

METHODS: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining.

RESULTS: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P<0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P<0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development.

CONCLUSION: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression.

Keywords: Stomach cancer; Celecoxib; Indomethacin; Cell kinetics