Effect of drugs on intracellular concentration of adriamycin in Ehrlich ascites carcinoma

Abstract

We studied the effects of test drugs on the influx and efflux of adriamycin in Ehrlich ascites carcinoma cells, by rapid and simple determinations of intracellular concentrations of adriamycin. Caffeine induced an increase in adriamycin accumulation and inhibited efflux. Biochemical modulators, aminobenzamide, ketoprofen and dipyridamole were also found to have inhibitory effect on adriamycin efflux. These test drugs had no effect on adriamycin influx from tumor cells. Caffeine amplified the inhibition of DNA biosynthesis induced by adriamycin under the efflux condition in vitro. Furthermore, caffeine significantly enhanced adriamycin concentration in the tumor in vivo. Thus, the combination of caffeine with adriamycin increased the antitumor activity of adriamycin. Therefore, the effect of caffeine on adriamycin concentration in vivo is consistent with that in vivo. These results suggest that caffeine is effective as biochemical modulator and our method in vivo is useful as the screening method of biochemical modulator.