Selective reversal of vinblastine resistance in multidrug-resistant cell lines by tamoxifen, toremifene and their metabolites.

In this study we describe the effects of tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites on the toxicity of a range of drugs to human breast and lung cancer and to Chinese hamster ovary cell lines, determined using a tetrazolium-based semi-automated colorimetric assay. Vinblastine resistance was completely abolished in an mdr1-transfected lung cancer cell line (S1/1.1), indicating that P-glycoprotein-mediated multidrug resistance can be fully reversed by anti-oestrogens. A substantial (14- to 39-fold) enhancement of vinblastine toxicity to highly multidrug-resistant (MCF-7Adr) cells expressing P-glycoprotein was also observed in the presence of tamoxifen, toremifene and their metabolites, while m-amsacrine, cisplatin and melphalan toxicity was unaffected.