Cyclooxygenases and colon cancer.
There is considerable interest in the involvement of cyclooxygenase-2 (COX-2) in colon carcinogenesis and its progression, because nonsteroidal anti-inflammatory drugs (NSAIDs) reduce mortality from colon cancer and COX-2 is one of the known targets of NSAIDs. COX-2 mRNA and protein levels are increased in colon cancer tissues from patients and in some colon cancer cell lines. The relationship between COX-2 and colon cancer is further confirmed by studies using the murine models of adenomatous polyposis coli, in which NSAIDs and gene knockouts reduce the number of spontaneously developing intestinal polyps. COX-2 expression in intestinal epithelial cells increases resistance to apoptosis, promotes tumor angiogenesis, and enhances invasion and metastasis. COX-2 expression in stromal cells appears to have a role in tumor angiogenesis because tumor growth is attenuated when colon cancer cells are implanted in COX-2 knockout mice due to a decreased vascular supply to the tumors. Although NSAIDs act via COX-2 to inhibit colon cancer growth, there also appear to be COX-2 independent actions for NSAIDs. COX-2 selective inhibitors can be the core drugs for the prevention and the treatment of colon cancer.
Kawai
Naoki
N
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
Tsujii
Masahiko
M
Tsuji
Shingo
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases