STUDIES ON EFFECTIVE REVERSAL OF ADRIAMYCIN—RESISTANT CHINESE HAMSTER OVARY CELL LINE BY VERAPAMIL

A noncytotoxie dose of verapamil (Ver) 3 μg/ml was found to potentiate 10-fold the growth—inhibitory effects of adriamycin (ADM) in ADM—resistant Chinese hamster ovary cell line (RC₁). Vet 3 μg/ml also reduced the IC₅₀ value of ADM from 1.2 μg/ml to 0.08 μg/ml in RC₁ in clonogenic assay. The index of reversing resistance was 15-fold. In an attempt to elucidate the mechanism of the reversion of the multidrug resistance by Vet, Ver in combination with ADM was found to enhance intracellular ADM accumulation in RC₁, and brought about more toxicity in RC₁ than ADM alone; and Vet in combination with ADM was shown to retard RC₁ in G₂+M phase by flow cytometry analysis.