Cyclooxygenase-independent inhibition of smooth muscle cell mitogenesis by ibuprofen

The aryl-propionic acid derivative, ketoprofen, has been shown to inhibit fibroblast growth by a cylooxygenase-dependent mechanism [Sánchez, T., Moreno, J.J., 1999. S(+) enantiomer inhibits prostaglandin production and cell growth in 3T6 fibroblast cultures. Eur. J. Pharmacol. 370, 63-67]. The present study demonstrates that ibuprofen, another aryl-propionic acid derivative, inhibited platelet-derived growth factor-BB (20 ng/ml)-induced mitogenesis of cultured bovine coronary artery smooth muscle cells in a stereo-independent manner. In addition, pretreatment of the cells with indomethacin (3 microM) did not affect the inhibitory effects of ibuprofen enantiomers on smooth muscle cell mitogenesis. Thus, aryl-propionic acid-type cyclooxygenase inhibitors can inhibit cell proliferation by both, cyclooxygenase-dependent and -independent ways.