MODULATION OF DOXORUBICIN-TOXICITY BY TAMOXIFEN IN MULTIDRUG-RESISTANT TUMOR-CELLS IN-VITRO AND IN-VIVO

Modulation of the resistance of tumors offers new strategies to improv e the therapeutical treatment of cancer. In this report, the anti-oest rogen tamoxifen was investigated in multidrug-resistant tumor cells in vitro and in vivo. The doxorubicin-resistance of L 1210/DOX-tumor cel ls, which express the multidrug-resistance phenotype, could be complet ely circumvented by addition of 1 mu g/ml tamoxifen. In contrast, no i ncreased effect could be observed in the parental L 1210 tumor cells o r in cytosine arabinoside-resistant L 1210 cells not expressing the mu ltidrug-resistance phenotype. Thus, the enhancing effect of tamoxifen was restricted only to the multidrug-resistant L 1210/DOX tumor cells. Similar to the in vitro experiments, a significant reduction in the g rowth in solid tumors of mice by the combined treatment of doxorubicin and tamoxifen was again observed only in the multidrug-resistant L 12 10/DOX tumors.