Antagonism between tamoxifen and doxorubicin in the MCF-7 human breast tumor cell line.
Tamoxifen, an antiestrogen, and doxorubicin, an anthracycline antibiotic, are each utilized alone and in combination in the treatment of breast carcinoma. In view of conflicting reports relating to the interaction between these drugs, studies were undertaken to characterize the influence of tamoxifen on growth inhibition by doxorubicin in the MCF-7 breast tumor cell line in vitro. Studies combining 5 microM tamoxifen, a clinically relevant concentration, with various concentrations of doxorubicin, indicated that this drug combination produces antiproliferative effects that appear to be less than additive. Concentration-dependent growth inhibition was analyzed further using various concentrations of tamoxifen and doxorubicin by the combination index-isobologram method; this quantitative approach provided clear evidence of antagonism between these agents, a finding with potential relevance to the treatment of breast cancer.
Woods
K E
KE
Department of Pharmacology/Toxicology, Medical College of Virginia, Richmond 23298.
Randolph
J K
JK
Gewirtz
D A
DA
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D004336:Drug Antagonism; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D013629:Tamoxifen; D004317:Doxorubicin