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 β-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 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.