Mechanisms of preventive effects of nonsteroidal anti- inflammatory drugs on colon carcinogenesis

We investigated the localization of cyclooxygenase(COX)-2，a possible target of nonsteroidal anti-inflammatory drugs(NSAIDs)in the prevention of colon carcinogenesis.Then effects of prostaglandins on vascular endothelial growth factor(VEGF)，an essential factor in tumor angiogenesis，production was studied.Results are as follows；a.High expression of COX-2was detected in sub-epithelial interstitial cells，possibly macrophages，broadly present in the surface area of human adenomas.b.Coz-2was only partly and weekly expressed in human advanced colon cancer.c.Prostaglandin(PG)E dramatically increased the production of VEGF by human macrophages but not by human colonic adenoma cells or cancer cells.d。This action was mediated by the increase of cAMP through EP I D 22 I D 2 and EP I D 24 I D 2 PGE receptorse.PGJ2，an agonist of nuclear receptor PPARγ，also dramatically increased VEGF production by human macrophages.These results suggest that PGs produced by macrophaged of human colonic adenomas may play important roles in human colon carcinogenesis through the induction of VEGF。NSAIDs possibly prevent human coloncarcinogenesis by the suppression of this step。

We investigated the localization of cyclooxygenase (COX)-2, a possible target of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colon carcinogenesis. Then effects of prostaglandins on vascular endothelial growth factor (VEGF), an essential factor in tumor angiogenesis, production was studied. Results are as follows;a. High expression of COX-2 was detected in sub-epithelial interstitial cells, possibly macrophages, broadly present in the surface area of human adenomas.b. Coz-2 was only partly and weekly expressed in human advanced colon cancer.c. Prostaglandin (PG) E dramatically increased the production of VEGF by human macrophages but not by human colonic adenoma cells or cancer cells.d. This action was mediated by the increase of cAMP through EPィイD22ィエD2 and EPィイD24ィエD2 PGE receptorse. PGJ2, an agonist of nuclear receptor PPAR γ, also dramatically increased VEGF production by human macrophages.These results suggest that PGs produced by macrophaged of human colonic adenomas may play important roles in human colon carcinogenesis through the induction of VEGF. NSAIDs possibly prevent human coloncarcinogenesis by the suppression of this step.