Prostaglandin levels in human colorectal mucosa: effects of sulindac in patients with familial adenomatous polyposis

Dig Dis Sci. 1998 Feb;43(2):311-6. doi: 10.1023/a:1018898120673.


Recent evidence suggests that nonsteroidal antiinflammatory drugs (NSAIDs) may prevent colorectal cancer. The mechanism of action of NSAIDs in chemoprevention is unknown but may be linked to their effect on mucosal prostaglandin levels. Levels of five major prostaglandin metabolites were measured by gas chromatography-mass spectrometry in biopsy specimens of flat rectal mucosa from four patients with familial adenomatous polyposis (FAP) before and after sulindac therapy and from five healthy individuals. The prostaglandin present at highest concentration in rectal mucosa from FAP and control subjects was prostaglandin E2. The concentration of thromboxane B2 alone was significantly elevated in FAP patients compared to controls (P = 0.016). In FAP patients treated with sulindac, all prostaglandin metabolite levels were significantly reduced compared to pretreatment levels (P < 0.05) except prostaglandin D2 (P = 0.07). Prostaglandins D2, E2, F2alpha, and 6-keto-F1alpha levels also were significantly reduced in FAP patients on sulindac compared to healthy controls (P < 0.05). However, interpatient heterogeneity of response to sulindac was evident with changes ranging from +19% to -89%, and the patient with the greatest reductions after sulindac developed colorectal cancer after 35 months of therapy. Sulindac treatment, at drug doses shown to regress colorectal adenomas in FAP patients, has heterogeneous effects on the level of major prostaglandins in their rectal mucosa and may not prevent colorectal cancer due to uncoupling of prostaglandin levels and carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / drug therapy
  • Adenomatous Polyposis Coli / metabolism*
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Colon
  • Dinoprost / analysis
  • Dinoprostone / analysis
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • Prostaglandin D2 / analysis
  • Prostaglandins / analysis*
  • Prostaglandins / metabolism
  • Prostaglandins F / analysis
  • Rectum
  • Sulindac / pharmacology*
  • Sulindac / therapeutic use
  • Thromboxane B2 / analysis


  • Anti-Inflammatory Agents, Non-Steroidal
  • Prostaglandins
  • Prostaglandins F
  • Sulindac
  • Thromboxane B2
  • Dinoprost
  • Dinoprostone
  • Prostaglandin D2
  • prostaglandin F1