Effect of cepharanthin and hyperthermia on the intracellular accumulation of adriamycin in the NIH3T3 cell lines transfected with oncogenes accompanied with pSV2neo vector.

The influence of several oncogenes on drug resistance has recently been show by transfection studies. Therefore, we investigated the influence of transfection on adriamycin (ADR) in cell line transfected with several oncogenes accompanied with pSV2neo vector. There were differences in both the intracellular accumulation of ADR and its sensitivity among the transfectants used in this study. There was a good correlation with the intracellular accumulation of ADR and its sensitivity (r = 0.76, P = 0.002). Further, there were no differences in the ADR efflux among the ras-family transfectants. Therefore, the changes in ADR sensitivity may be due to changes in ADR influx. On the other hand, the ADR accumulation showed an increase of 1.14-1.29 fold by the treatment of 10 micrograms/ml CEP. Moreover, the ADR accumulation showed an increase of 1.29-3.11 fold by hyperthermia at 42 degrees C. There was no significant difference in the ADR accumulation at 42 degrees C among the transfectants, suggesting that the influence on the ADR accumulation may be counteracted by hypethermia at 42 degrees C.