Flufenamic acid: Growth modulating effects on human aortic smooth muscle cells in vitro

PURPOSE The aim of the study was to examine the effects of flufenamic acid on proliferation, clonogenic activity, migratory ability, cell-cycle distribution, and p44/42-mitogen-activated protein kinase (MAPK) expression on serum-stimulated human aortic smooth muscle cells (haSMCs) in vitro. MATERIALS AND METHODS HaSMCs were treated with flufenamic acid in three different doses (40 μmol/L, 200 μmol/L, 400 μmol/L) for 4 days, and then flufenamic-acid-free culture medium was supplemented every 4 days until day 20 after initial treatment. The growth kinetics were assessed. Cell-cycle analysis was performed by flow cytometry. The clonogenic activity was evaluated with use of colony formation assays. The migratory ability was investigated by stimulation with platelet derived growth factor (PDGF-BB) in 24 well plates with 8-μm pore membrane inserts. The p44/42 MAPK was detected by Western blot technique. RESULTS Flufenamic acid inhibited the proliferation (400 μmol/L treatment over 4 d; 179,700 ± 49,800 vs 747,900 ± 144,000; P P P P P CONCLUSION Flufenamic acid inhibits the proliferation and migration of haSMCs. Further experiments with animal models concerning stenosis and restenosis are necessary to evaluate the potential of this promising drug.