Sulindac reversal of 15-PGDH-mediated resistance to colon tumor chemoprevention with NSAIDs.

ABSTRACT: 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 h

SUBMITTER: Fink SP 

PROVIDER: S-EPMC4322189 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature