Non‐steroidal anti‐inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model ¹

Abstract

Cyclooxygenase-2 inhibitors are potentially ideal chemopreventive agents as they inhibit ACF and are not gastrotoxic.

Celecoxib Treatment Alters the Gene Expression Profile of Normal Colonic Mucosa

“…ACFs are considered to be an early preneoplastic lesion in the colon (75), and the ability to decrease the frequency of ACF after carcinogen treatment is used routinely in experimental models of colon cancer to estimate the cancer preventive effect of different agents (76). It is particularly well established that NSAIDs (77)(78)(79) and celecoxib (80)(81)(82)(83) decrease the frequency of carcinogen-induced ACFs in the colon in animal models. It has also been shown that the number of ACF in patients who received sulindac sulfide is decreased (84).…”

Gene Expression Patterns Distinguish Colonoscopically Isolated Human Aberrant Crypt Foci from Normal Colonic Mucosa

“…It is known that nonsteroidal anti-inflammatory drugs, and particularly celecoxib, decrease the frequency of ACF in humans as well as in rodent models of carcinogen-induced colon cancer (67)(68)(69)(70). We compared the changes in gene expression found in normal descending colonic mucosa of patients treated with celecoxib for 1 year (71) to the differences seen in gene expression between ACF and NM from the descending colon.…”

Chemopreventive Strategies Using NSAIDs and COX-2 Inhibitors

“…These include sulindac, indomethacin, piroxicam, aspirin, and ibuprofen, and the selective COX-2 inhibitors celecoxib, rofecoxib, nabumetone and meloxicam. [32][33][34]38,[46][47][48]53,54,66,67,74,[120][121][122] A dosedependent effect of NSAIDs and COX-2 inhibitors exists against both the initiation and promotion of the adenoma-carcinoma sequence, and pre-existing tumors. Of note, there are regional differences in sensitivity for chemopreventive treatment.…”