Cyclooxygenase-2 (COX-2) in carcinogenesis and selective cox-2 inhibitors for chemoprevention in gastrointestinal cancers

被引:27
作者
Fujimura T. [1 ]
Ohta T. [1 ]
Oyama K. [1 ]
Miyashita T. [1 ]
Miwa K. [2 ]
机构
[1] Kanazawa University Hospital, Kanazawa
[2] Toyama Rosai Hospital, Uozu
关键词
Colorectal cancer; Cyclooxygenase-2 (COX-2); Esophageal cancer; Gastric cancer; Selective COX-2 inhibitors (Coxibs);
D O I
10.1007/s12029-008-9035-x
中图分类号
学科分类号
摘要
Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have a property to inhibit tumor development in some cancers while it shows various side effects such as gastrointestinal bleeding and renal disorder. Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were originally developed as one of anti-inflammatory drugs to avoid side effect of NSAIDs. Fortunately, the coxibs was also proved to have an inhibiting effect on tumorigenesis by many experimental studies using cell lines and animal models like NSAIDs. Discussion: Since a randomized study for polyp chemoprevention by celecoxib in familial adenomatous polyposis (FAP) patients demonstrated a significant reduction in the number of colorectal polyps, the clinical use of celecoxib was approved for FAP patients. Three large trials using celecoxib (the Adenoma Prevention with Celebrex and the Prevention of Spontaneous Adenomatopus Polyps) or refecoxib (the Adenomatous Polyp Prevention on Vioxx) for the recurrence of colorectal polyps in patients with a history of colorectal adenoma polypectomized confirmed chemopreventive effects on colorectal adenoma but two of three trails alerted us a hazard of cardiovascular (CV) events. Thereafter, some coxibs were withdrawn from the market because they showed to increase risk of serious CV events including heart attacks and strokes. But recent reports concluded that a merit of the reduction in gastrointestinal events by coxibs exceeded a demerit of the increase in serious CV events. In this review, a role of COX-2 in carcinogenesis of gastrointestinal tract and a future of coxibs for chemoprevention are discussed © 2008 Humana Press Inc.
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页码:78 / 82
页数:4
相关论文
共 36 条
[1]  
Pai R., Soreghan B., Szabo I.L., Pavelka M., Baatar D., Tarnawski A.S., Prostaglandin E2 transactivates EGF receptor: A novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy, Nat Med., 8, pp. 289-93, (2002)
[2]  
Tsujii M., Dubois R.N., Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2, Cell., 83, pp. 493-501, (1995)
[3]  
Sharma S., Stolina M., Yang S.C., Baratelli F., Lin J.F., Atianzar K., Luo J., Zhu L., Lin Y., Huang M., Dohadwala M., Batra R.K., Dubinett S.M., Tumor cyclooxygenase 2-dependent suppression of dendritic cell function, Clin Cancer Res., 9, pp. 961-68, (2003)
[4]  
Tsujii M., Kawano S., Tsuji S., Sawaoka H., Hori M., Dubois R.N., Cyclooxygenase regulates angiogenesis induced by colon cancer cells, Cell., 93, pp. 705-16, (1998)
[5]  
Li G., Yang T., Yan J., Cyclooxygenase-2 increased the angiogenic and metastatic potential of tumor cells, Biochem Biophys Res Commun., 299, pp. 886-90, (2002)
[6]  
Tsujii M., Kawano S., Dubois R.N., Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential, Proc Natl Acad Sci U S A., 94, pp. 3336-40, (1997)
[7]  
Morris C.D., Armstrong G.R., Bigley G., Green H., Attwood S.E., Cyclooxygenase-2 expression in the Barrett's metaplasia-dysplasia- adenocarcinoma sequence, Am J Gastroenterol., 96, pp. 990-96, (2001)
[8]  
Kauer W.K., Peters J.H., Demeester T.R., Ireland A.P., Bremner C.G., Hagen J.A., Mixed reflux of gastric and duodenal juice is more harmful to the esophagus than gastric juice alone. the need for surgical therapy re-emphasized, Ann Surg., 222, pp. 525-33, (1995)
[9]  
Stein H.J., Barlow A.P., Demeester T.R., Hinder R.A., Complications of gastroesophageal reflux disease: Role of the lower esophageal sphincter, esophageal acid acid/alkaline exposure and duodenogastric reflux, Ann Surg., 216, pp. 35-43, (1992)
[10]  
Zhang F., Altorki N.K., Wu Y.C., Soslow R.A., Subbaramaiah K., Dannenberg A.J., Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: Evidence for involvement of bile acids, Gastroenterology., 121, pp. 1391-99, (2001)