title: A dual-inhibition study on vascular smooth muscle cells with meclofenamic acid and β-irradiation for the prevention of restenosis.
abstract: OBJECTIVE
  Restenosis is still one of the major limitations after angioplasty. A therapeutic treatment combining β-irradiation and pharmacologic cyclooxygenase-2 inhibition was employed to study the impact on vascular smooth muscle cells (SMCs).
  
  
  METHODS
  The effects of meclofenamic acid in combination with yttrium-90 ((90)Y) on cell growth, clonogenic activity, cell migration, and cell cycle distribution of human aortic SMCs were investigated. Treatment was sustained over a period of 4 days and recovery of cells was determined until day 20 after initiation. The hypothesis was that there is no difference between control and treated groups.
  
  
  RESULTS
  A dose-dependent growth inhibition was observed in single and combined treatment groups for meclofenamic acid and β-irradiation. Cumulative radiation dosage of 8 Gy completely inhibited colony formation. This was also observed for 200 μM meclofenamic acid alone or in combination with minor β-irradiation dosages. Results of the migration tests showed also a dose dependency with additive effects of combined therapy. Meclofenamic acid 200 μM alone and with cumulative β-irradiation dosages resulted in an increased G2/M-phase share.
  
  
  CONCLUSIONS
  Incubating human SMCs with meclofenamic acid and (90)Y for a period of 4 d (ie, 1.5 half-life times) resulted in an effective inhibition of smooth muscle cell proliferation, colony formation, and migration.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, WaldhÖrnlestr. 22, 72072 Tübingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sauter
authors.forename: Alexis
authors.initials: A
authors.lastname: Landers
authors.forename: Helmut
authors.initials: H
authors.lastname: Dittmann
authors.forename: Maren
authors.initials: M
authors.lastname: Pritzkow
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wiesinger
authors.forename: Melanie
authors.initials: M
authors.lastname: Bayer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Bantleon
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmehl
authors.forename: Claus D
authors.initials: CD
authors.lastname: Claussen
authors.forename: Rainer
authors.initials: R
authors.lastname: Kehlbach
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001918:Brachytherapy; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003251:Constriction, Pathologic; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D055502:Secondary Prevention; D013997:Time Factors; D015021:Yttrium Radioisotopes
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D015021:Yttrium Radioisotopes; D008469:Meclofenamic Acid