Schober Wolfgang, Kehlbach Rainer, Gebert Regina, Wiskirchen Jakub, Rodegerdts Enno, Claussen Claus D, Duda Stephan H
Department of Diagnostic Radiology, Eberhard-Karls-Universitat, Hoppe-Seyler-Strasse 3, D-72076 Tubingen, Germany.
Cardiovasc Intervent Radiol. 2002 Jan-Feb;25(1):57-63. doi: 10.1007/s00270-001-0077-8. Epub 2002 Jan 17.
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.
本研究旨在探讨甲氯芬那酸对血清刺激的人主动脉平滑肌细胞（haSMCs）增殖、克隆形成活性、迁移能力、细胞周期分布及p44/42丝裂原活化蛋白激酶（MAPK）表达的影响。
将haSMCs用三种不同浓度（10 mM、100 mM、200 mM）的甲氯芬那酸处理4天。然后补充不含甲氯芬那酸的培养基直至第20天。评估生长动力学。通过流式细胞术进行细胞周期分析。用集落形成试验评估克隆形成活性。在带有8毫米孔膜插入物的24孔板中用血小板衍生生长因子（PDGF-BB）刺激来研究迁移能力。通过蛋白质印迹技术检测p44/42 MAPK。
甲氯芬那酸以剂量依赖方式抑制haSMCs的增殖、克隆形成活性和迁移能力。细胞周期分析显示G2/M期阻滞。p44/42 MAPK显著降低。
甲氯芬那酸抑制haSMCs的增殖和迁移。如果能以足够剂量全身应用或通过局部给药，甲氯芬那酸可能是预防血管成形术后再狭窄的一种有价值的物质。
