Therapeutic treatment of DMBA-induced mammary tumors with PPAR ligands

The objective of this study was to evaluate the ability of troglitazone (a thiazolidinedione) and Wy-14,643 (a clofibrate) to inhibit progression of n on-detectable and detectable mammary tumors in rats induced by 7,12 dimethy lbenz(a)anthracene (DMBA) when compared to those receiving no treatment or tamoxifen. Although not as effective as tamoxifen in decreasing overall tum or incidence, Wy-14,643 reduced the percentage and number of malignant tumo rs that developed when compared to both troglitazone and control. Treatment of detectable tumors with either Wy-14,643 or troglitazone induced regress ion or stasis of total tumor volume in 40-50% of the animals, compared to o nly 10% in control and 65% in tamoxifen treated animals. Moreover, each PPA R ligand was as effective as tamoxifen in preventing additional tumor devel opment. In summary, both PPAR ligands were more effective than no treatment in preventing tumor progression once detected. However, only the PPAR-alph a activator, Wy-14,643 was able to reduce the development of malignant tumo rs when administered prior to detection.