In Vitro Combination Chemotherapy Demonstrating Potentiation of Vincristine Cytotoxicity by Prednisolone

Human lymphoid cells grown in long-term tissue culture have been used to study the cytotoxic effects of the combination of vincristine and prednisolone. The potentiating effects of this drug combination in vitro cannot be consistently shown if the drugs are added without attention to the growth rate of the cultured population. If the cultured cells have achieved maximum density and have remained at this density for more than 24 hr, they are readily killed by vincristine alone and no further kill is achieved by adding prednisolone. Rapidly growing cell cultures, however, are relatively resistant to vincristine. The addition of prednisolone to such cultures restores their sensitivity to vincristine, but the combination is no more effective than is vincristine alone in stable cell populations. These findings indicate that the effects of vincristine on the mitotic spindle, which produce metaphase arrest, do not account entirely for its ability to destroy cells. A second mechanism of action of vincristine at low concentrations is proposed.