A Dual-inhibition Study on Vascular Smooth Muscle Cells with Meclofenamic Acid and β-irradiation for the Prevention of Restenosis

PURPOSE: Restenosis is still one of the major limitations after angioplasty. A therapeutic treatment combining beta-irradiation and pharmacologic cyclooxygenase-2 inhibition was employed to study the impact on vascular smooth muscle cells (SMCs). MATERIALS AND 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 beta-irradiation. Cumulative radiation dosage of 8 Gy completely inhibited colony formation. This was also observed for 200 mu M meclofenamic acid alone or in combination with minor beta-irradiation dosages. Results of the migration tests showed also a dose dependency with additive effects of combined therapy. Meclofenamic acid 200 mu M alone and with cumulative beta-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.