Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: a review and report of personal experience.
Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However,coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis (FAP),which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration (FDA) immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum,and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.
Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. tphuji@surg2.m.kanazawa-u.ac.jp
Takashi
T
Fujimura
Tetsuo
T
Ohta
Katsunobu
K
Oyama
Tomoharu
T
Miyashita
Koichi
K
Miwa
D011125:Adenomatous Polyposis Coli / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000209:etiology / Q000517:prevention & control; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000209:etiology / Q000517:prevention & control; D005770:Gastrointestinal Neoplasms / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology / Q000517:prevention & control
D052246:Cyclooxygenase 2 Inhibitors; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D015232:Dinoprostone