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The ability of the anti-oestrogens tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites to modify doxorubicin (dox) toxicity to intrinsically resistant and multidrug resistant cell lines was compared, using human breast and lung cancer, and Chinese hamster ovary cell lines. The anti-oestrogens significantly enhanced dox toxicity to multidrug resistant, P-glycoprotein-positive cell lines, but did not affect toxicity to intrinsically resistant, P-glycoprotein-negative cells. Modification was observed at clinically achievable anti-oestrogen concentrations. Toremifene and tamoxifen would therefore appear to be good candidates for in vivo studies as MDR modulating agents in selected patients with P-glycoprotein-positive tumours.

Original publication

DOI

10.1038/bjc.1993.224

Type

Journal article

Journal

Br J Cancer

Publication Date

06/1993

Volume

67

Pages

1189 - 1195

Keywords

ATP Binding Cassette Transporter, Subfamily B, Member 1, Animals, Antibodies, Monoclonal, Breast Neoplasms, CHO Cells, Carrier Proteins, Cell Division, Cricetinae, Doxorubicin, Drug Interactions, Drug Resistance, Drug Screening Assays, Antitumor, Epitopes, Estrogen Antagonists, Humans, Lung Neoplasms, Membrane Glycoproteins, Tamoxifen, Toremifene, Tumor Cells, Cultured