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 improve the therapeutical treatment of cancer. In this report, the anti-oestrogen tamoxifen was investigated in multidrug-resistant tumor cells in vitro and in vivo. The doxorubicin-resistance of L 1210/DOX-tumor cells, which express the multidrug-resistance phenotype, could be completely circumvented by addition of 1 microgram/ml tamoxifen. In contrast, no increased effect could be observed in the parental L 1210 tumor cells or in cytosine arabinoside-resistant L 1210 cells not expressing the multidrug-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 growth in solid tumors of mice by the combined treatment of doxorubicin and tamoxifen was again observed only in the multidrug-resistant L 1210/DOX tumors.