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

• Published in: Cardiovascular and interventional radiology 2002-01, Vol.25 (1), p.57-63
• Main Authors: SCHÖBER, Wolfgang, KEHLBACH, Rainer, GEBERT, Regina, WISKIRCHEN, Jakub, RODEGERDTS, Enno, CLAUSSEN, Claus D, DUDA, Stephan H
• Format: Article
• Language: English
• Subjects: Acids; Angioplasty; Aorta; Biological and medical sciences; Cardiovascular system; Cell culture; CELL CYCLE; Cell Cycle - drug effects; Cell Division - drug effects; Cell migration; Cell Movement - drug effects; Cell proliferation; Cells, Cultured; COLONY FORMATION; Cyclooxygenase Inhibitors - pharmacology; Drug delivery; DRUGS; Flow cytometry; Growth factors; Growth kinetics; Humans; IN VITRO; In Vitro Techniques; INHIBITION; Inserts; Kinases; MAP kinase; Meclofenamic Acid - pharmacology; Medical sciences; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; MUSCLES; Pharmacology. Drug treatments; Platelet-derived growth factor; Platelet-derived growth factor BB; Protein kinase; PROTEINS; RADIOLOGY AND NUCLEAR MEDICINE; Restenosis; Smooth muscle; Vascular wall
• ISSN: 0174-1551; 1432-086X
• DOI: 10.1007/s00270-001-0077-8

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). 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. 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. 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.