α1-acid glycoprotein and multidrug resistance

This investigation describes the effect of the acute phase protein, a(1)-acid glycoprotein (AGP) on vincristine binding, vincristine accumulation and the chemosensitizing action of dexverapamil. The studies were carried out using tritium-labelled vincristine in both cell-lines and leukemia cells isolated from patients. The stimulatory effect of dexverapamil (10 mu g/ml) on vincristine accumulation (80 pg/million cells) was seen in both sensitive and vincristine resistant cell lines. This effect could be completely blocked by AGP (1-4 mg/ml). The binding of vincristine to AGP (60%) was reduced 50% by dexverapamil (10 mu g/ml). It is concluded that interactions between dexverapamil and vincristine at binding sites on AGP modulate the chemosensitizer effect of dexverapamil and that AGP may impair the chemosensitizer effect of dexverapamil in patients with high AGP plasma levels.