Modification by hyperthermia and cepharanthine of the Killing effect of adriamycin on NIH 3T3 cells

The cytotoxic effect of anticancer agents depends markedly on the intracellular uptake of the anticancer drug; its maintenance is increased by accelerating the intracellular uptake of anticancer agent and inchbiting. Using with flow-cytometry, we demonstrated that the intracellular uptake of adriamycin (ADM) is increased by hyperthermia, and that cepharanthine (CEP) and Verapamil inhibit its retention. We investigated the cytotoxic effect of the combination of ADR, CEP and hyperthermia, using a NIH3T3 cell line. The cytotoxic effect of ADR is increased by hyperthermia; its effect is acquired at a lower temperature which has no cytotoxic effect alone. With the conbination of CEP, ADR and hyperthermia, the cytotoxic effect is further increased. The synergism is increased by the elevation of temperature and a long of exposure time of CEP. The increase of the intracellular accumulation anticanceragent is important to overcome multidrugresistance, a phenomenon which has that attracted agreat deal of attention.