Long‐lasting Accumulation of Vinblastine in Inostamycin‐treated Multidrug‐resistant KB Cells

Inostamycin, a novel polyether compound, reverses multidrug resistance in KB cells. The mechanism of its action was studied by use of radioactively labeled vinblastine. Inostamycin dose‐dependently increased the accumulation of [(3)H] vinblastine in multidrug‐resistant KB‐C4 cells at 0.5‐2 μg/ml, while it did not enhance accumulation in the drug‐sensitive KB‐3‐1 cells. At a concentration of 1 μ/ ml inostamycin inhibited active [(3)H] vinblastine efflux from KB‐C4 cells, but not from KB‐3‐1 cells, and inhibited [(3)H] vinblastine binding to KB‐C4 membranes with an IC(5O) of 0.94 μg/ml (1.3 μM). Furthermore, [(3)H] vinblastine accumulated by treatment with 1 /μg/ml of inostamycin was resistant to efflux from KB‐C4 cells, even after the removal of inostamycin.