Selective COX-2 inhibition affects fatty acids, but not COX mRNA expression in patients with FAP

Abstract

Familial adenomatous polyposis (FAP) provides a model for sporadic colorectal cancer development. Cyclooxygenase (COX) inhibition may ameliorate polyp development, but rofecoxib was withdrawn due to cardiovascular side effects. Although this selective COX-2 inhibitor, like diet, may alter the fatty acid and eicosanoid pattern, data on the potential alteration in tissues after use, are scarce. The aims were to study if rofecoxib might influence the fatty acid distribution in serum phospholipids and duodenal lesions, mRNA for COX-1 and COX-2 in leucocytes and duodenal lesions, and finally plasma levels of PGE2 in a randomized, double-blind, placebo controlled study (n = 38). Significant reductions were found for essential fatty acid index both in serum phospholipids (P = 0.01, 95% CI = −0.9; −0.1), and in duodenal lesions (P = 0.04, 95 CI % = −0.9; −0.1) after treatment. No treatment effects were found on the COX mRNA expression, or in the plasma PGE2 levels. Dietary AA/EPA ratio was inversely associated with all the indicators of EFA status (all P < 0.01). These findings suggest that the effects of COX chemoprevention should be further investigated in FAP and that dietary needs should be included in the treatment of FAP.

FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

“…Previous reports support the present finding that PGE2 content is not changed upon decreasing COX-2 expression (31)(32)(33)(34)(35). A number of authors have demonstrated that in the Vhl ∆IE /Apc min / + intestinal tumor model, the production of PGE2 is not dependent on the levels of COX-2, since despite the blockage of COX-2 activity by nimesulide, the PGE2 content remained elevated, suggesting that the high PGE2 levels observed were due to an increase in mPGES1 expression (31,32).…”

“…In addition, mPGES1 has been observed to be increased in CRC tumor tissues and to correlate with a worse prognosis (34). Almendingen et al (35) reported that treatment with rofecoxib, a COX-2 selective inhibitor, did not affect the PGE2 levels in plasma of patients with familial adenomatous polyposis. Altogether, those findings offer an explanation for the present results.…”

Relationship between Fecal Content of Fatty Acids and Cyclooxygenase mRNA Expression and Fatty Acid Composition in Duodenal Biopsies, Serum Lipoproteins, and Dietary Fat in Colectomized Familial Adenomatous Polyposis Patients

“…Colectomized familial adenomatous polyposis patients had a deviant fatty acid profile with high levels of arachidonic acid and docosahexaenoic acid and low levels of linoleic acid and alpha-linolenic acid in serum phospholipids, which is in accordance with studies in patients with other types of cancers [5, 10–13]. In a previous familial adenomatous polyposis study [14], comparable treatment effects of a cyclooxygenase-2 inhibitor were observed on the fatty acid composition in serum phospholipids and duodenal lesions, presumably and most importantly the nonbeneficial effects involving essential fatty acids. …”

Role of anti‐inflammatory interventions in high‐fat‐diet‐induced obesity

“…This result can be explained by the allosteric regulation of COXs by FAs. COXs are inhibited by celecoxib and this can help reduce the AA‐to‐EPA ratio (Almendingen et al, , ; Dong et al, ). Furthermore, upregulated expression of COX‐2 was observed in several metabolic disorders including obesity and NAFLD.…”

“…This result can be explained by the allosteric regulation of COXs by FAs. COXs are inhibited by celecoxib and this can help reduce the AA-to-EPA ratio (Almendingen et al, 2007(Almendingen et al, , 2010Dong et al, 2016).…”