Unilamellar lipid vesicles have been used as a carrier vehicle to enhance the uptake of actinomycin D into an actinomycin D resistant Chinese hamster tumor cell line (DC 3F/ADX). The DC 3F/ADX cell line is resistant to actinomycin D as a result of its decreased capacity to transport actinomycin D across the plasma membrane and its able to grow in the presence of concentrations of actinomycin D that are cytotoxic for the sensitive parent cell line (DC 3F). Incubation of resistant DC 3F/ADX cells with actinomycin D containing vesicles produced a 5 fold increase in intracellular drug concentration over that achieved by exposure to identical concentrations of the drug added to the culture medium. Vesicle mediated uptake of actinomycin D into resistant cells produced inhibition of cellular RNA synthesis and cell growth at actinomycin D concentrations that had no inhibitory effect when added as free drug in the culture medium. Dose response measurements established that direct introduction of actinomycin D into resistant cells by means of lipid vesicles resulted in a 200 fold reduction in the concentration of actinomycin D required to inhibit cellular RNA synthesis and a 120 fold reduction in the dose of actinomycin D required to produce a 50% inhibition of cell growth. These results lend strong support to the hypothesis that cellular resistance to actinomycin D is due to a lower capacity to take up actinomycin D as a result of a reduction in the permeability of the cellular plasma membrane to this drug. The potential value of lipid vesicles for introducing other classes of drugs into cultured cells and their possible use in chemotherapy are also discussed.
|Original language||English (US)|
|State||Published - Dec 1 1976|
ASJC Scopus subject areas
- Cancer Research