Peroxisome proliferator-activated receptor δ as a molecular target to regulate lung cancer cell growth

It has been assumed that prostaglandin (PG)12 signaling contributes to the negative growth control of lung cancer cells; however, the mechanism remains unresolved. PGI(2) functions through a cell surface G protein-coupled receptor (prostaglandin I2-binding receptor, IP) and also exerts an effect by interacting with a nuclear hormone receptor, peroxisome proliferator-activated receptor delta (PPAR delta). We found that PPAR delta was a key molecule of PGI(2) signaling to give negative growth control of lung cancer cells (A549), using carbarprostacyclin, a PGI(2) agonist for IP and PPAR delta, and L-165041, a PPAR delta agonist. Furthermore, PPAR delta-induced cell growth control was reinforced by the inhibition of cyclooxygenase. These results suggest that PPAR delta activation under the suppression of PG synthesis is important to regulate lung cancer cell growth. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.