Involvement of prostaglandin E2 in bile acid-caused promotion of colon carcinogenesis and anti-promotion by the cyclooxygenase inhibitor indomethacin.
The mechanism of the anti-promoting effect of the prostaglandin (PG) synthesis inhibitor indomethacin in colon carcinogenesis was investigated. Male Sprague-Dawley rats received 0.002% water solution of indomethacin as drinking water freely for 3 days, then a subcutaneous injection of various doses of PGE2 and/or an intrarectal instillation of 12 mumol of sodium deoxycholate as a colon tumor promoter. Ornithine decarboxylase (ODC), a marker of tumor promotion, in the distal colonic mucosa was assayed at 4 hr after deoxycholate instillation. Indomethacin significantly suppressed the deoxycholate-augmented increase of ODC activity, while exogenous PGE2 restored or further increased the augmented ODC activity. The amount of PGE2 and the level of ODC activity were well correlated. However, PGE2 alone without deoxycholate did not increase the activity. Deoxycholate markedly increased colonic mucosal PGE2 at 1 hr after the instillation, and indomethacin decreased it. The results indicate that PGE2, the production of which is stimulated in the colonic mucosa by deoxycholate, is involved in the induction of colonic mucosal ODC. This is probably why PG synthesis inhibitors may inhibit the tumor promotion and prevent cancer development in the colon.
D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000633:toxicity*; D015232:Dinoprostone; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D011458:Prostaglandins E / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D003840:Deoxycholic Acid; D015232:Dinoprostone; D007213:Indomethacin