Review article: COX-2, prostanoids and colon cancer.
Epidemiological, experimental, and clinical studies have demonstrated that colon carcinogenesis may be prevented by nonsteroidal anti-inflammatory drugs (NSAIDs). Although controversy remains, recent studies, including ours, have revealed that NSAIDs suppress colon carcinogenesis at the adenoma stage where cyclooxygenase-2 (COX-2), a major molecular target in this action, is mainly expressed in interstitial cells but not in tumour cells. Therefore, it is unlikely that NSAIDs prevent colon cancer formation through modulating the functions of tumour cells. A more possible assumption is that NSAIDs suppress colon carcinogenesis through the inhibition of prostaglandin formation. However, the mechanisms by which prostanoids promote colon carcinogenesis have not been elucidated to date. A prostanoids act through both membrane receptors and nuclear receptors such as peroxisome proliferator receptor (PPAR) gamma or delta, one focus in this area is to investigate their roles in colon carcinogenesis, including the induction of growth factors.
Ota
S
S
Third Department of Internal Medicine, Saitama Medical School, Moroyama-machi, Iruma-gum, Japan. ota@saitama-med.ac.jp
Bamba
H
H
Kato
A
A
Kawamoto
C
C
Yoshida
Y
Y
Fujiwara
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases