Meclofenamic acid for inhibition of human vascular smooth muscle cell proliferation and migration:: An in vitro study

Purpose: The aim of the study was to examine the effects of meclofenamic acid on proliferation, clonogenic activity, migratory ability, cell cycle distribution and p44/42 MAPK (mitogen activated protein kinase) expression in serum-stimulated human aortic smooth muscle cells (haSMCs). Methods: haSMCs were treated with meclofenamic acid in three different concentrations (10 muM, 100 muM, 200 muM) for 4 days. Then meclofenamic acid-free culture medium was supplemented until day 20. Growth kinetics were assessed. Cell cycle analysis was performed by flow cytometry. Clonogenic activity was evaluated with colony formation assays. Migratory ability was investigated by stimulation with platelet-derived growth factor (PDGF-BB) in 24-well plates with 8 mum pores membrane inserts. p44/42 MAPK was detected by Western blot technique. Results: Meclofenamic acid inihibited the proliferation, clonogenic activity and migratory ability of haSMCs in a dose-dependent manner. Cell cycle analysis revealed a G2/M-phase block. The p44/42 MAPK was significantly reduced. Conclusion: Meclofenamic acid inhibits the proliferation and migration of haSMCs. If a sufficient dose, of meclofenamic acid can be applied systemically or by local drug delivery it could be a valuable substance to prevent restenosis after angioplasty.