biostudies-literatureFink SPNCI NIH HHS291-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4322189biostudies-literatureUnknown36(2)Non-steroidal anti-inflammatory drugs prevent colorectal cancer by inhibiting cyclooxygenase (COX) enzymes that synthesize tumor-promoting prostaglandins. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor that degrades tumor-promoting prostaglandins. Murine knockout of 15-PGDH increases susceptibility to azoxymethane-induced colon tumors. It also renders these mice resistant to celecoxib, a selective inhibitor of inducible COX-2 during colon neoplasia. Similarly, humans with low colonic 15-PGDH are also resistant to colon adenoma prevention with celecoxib. Here, we used aspirin and sulindac, which inhibit both COX-1 and COX-2, in order to determine if these broader COX inhibitors can prevent colon tumors in 15-PGDH knockout (KO) mice. Unlike celecoxib, sulindac proved hCarcinogenesisSulindac reversal of 15-PGDH-mediated resistance to colon tumor chemoprevention with NSAIDs.PMC4322189N01 CN-43302P50 CA150964Dawson DMMarkowitz SDZhang YYang PKresak AChen YWillis JEKopelovich LBarnholtz-Sloan JSFink SPLawrence EGfalseSulindac reversal of 15-PGDH-mediated resistance to colon tumor chemoprevention with NSAIDs.Non-steroidal anti-inflammatory drugs prevent colorectal cancer by inhibiting cyclooxygenase (COX) enzymes that synthesize tumor-promoting prostaglandins. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor that degrades tumor-promoting prostaglandins. Murine knockout of 15-PGDH increases susceptibility to azoxymethane-induced colon tumors. It also renders these mice resistant to celecoxib, a selective inhibitor of inducible COX-2 during colon neoplasia. Similarly, humans with low colonic 15-PGDH are also resistant to colon adenoma prevention with celecoxib. Here, we used aspirin and sulindac, which inhibit both COX-1 and COX-2, in order to determine if these broader COX inhibitors can prevent colon tumors in 15-PGDH knockout (KO) mice. Unlike celecoxib, sulindac proved h2015-01-01T00:00:00Z2015 Feb2025-04-21T22:25:38.496Z2019-03-27T01:44:54ZS-EPMC43221892550393010.1093/carcin/bgu241