Failure of indomethacin to inhibit growth of the R3230AC mammary tumor in rats.

The relationship between the dietary lipid-induced growth of the R3230AC mammary tumor and prostaglandin E2 (PGE2) levels as well as the effect of the prostaglandin synthetase inhibitor indomethacin (Ind) on these parameters was examined. F344 rats fed a high-fat (HF) diet containing 20% corn oil demonstrated more rapid tumor growth and higher tumor and plasma PGE2 levels than rats fed a 20% hydrogenated cottonseed oil (HCTO) diet. Addition of 0.004% Ind to the HF diet markedly reduced tumor and plasma PGE2 levels. However, Ind had no effect on tumor growth. Neither the fatty acid composition nor the insulin-binding capacity of the tumor plasma membranes was affected by Ind. Membranes from animals fed HF diets with or without Ind bound more 125I-labeled insulin than membranes from HCTO-fed rats. The results suggest that, for the R3230AC mammary tumor, reduction in both tumor and plasma PGE2 levels by Ind did not result in reduced tumor growth in animals fed diets high in polyunsaturated fatty acids.