Meclofenamic acid for inhibition of human vascular smooth muscle cell proliferation and migration: an in vitro study.
OBJECTIVE
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 mM, 100 mM, 200 mM) 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 mm pores membrane inserts. p44/42 MAPK was detected by Western blot technique.


RESULTS
Meclofenamic acid inhibited 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.


CONCLUSIONS
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.
Schober
Wolfgang
W
Department of Diagnostic Radiology, Eberhard-Karls-Universitat, Hoppe-Seyler-Strasse 3, D-72076 Tubingen, Germany. Schober.wogi@t-online.de
Kehlbach
Rainer
R
Gebert
Regina
R
Wiskirchen
Jakub
J
Rodegerdts
Enno
E
Claussen
Claus D
CD
Duda
Stephan H
SH
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D008469:Meclofenamic Acid