Oestrogen receptor status and the response of human breast cancer cell lines to a combination of methotrexate and 17-beta oestradiol.
We have investigated the modifying influence of 17-beta oestradiol (E2), on the cytotoxicity of methotrexate (MTX) towards two cell lines derived from human breast carcinoma. E2 (10(-7) M-10(-6) M) significantly reduced the antimetabolic effects of the drug towards an E2 non-responsive cell line, MDA-MB-436, whilst potentiating the action of MTX in an E2 responsive line, MCF-7. Similarly, E2 (10(-6) M) partially reversed the anti-proliferative effects of MTX in the MDA-MB-436 line and potentiated growth inhibition in the E2 responsive cells. This potentiation was not observed if E2 was replaced by the less biologically active alpha-isomer. In both cell lines pharmacological concentrations of the E2 reduced intracellular levels of MTX achieved during a 48 h treatment period. The latter finding is consistent with the ability of E2 to protect MDA-MB-436 cells from the action of MTX. Potentiation of the effects of MTX towards MCF-7 cells occurs despite reduced intra-cellular drug levels.
D001943:Breast Neoplasms / Q000032:analysis / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003857:Deoxyuridine / Q000378:metabolism; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D011959:Receptors, Estradiol / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*
D004273:DNA, Neoplasm; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D004958:Estradiol; D003857:Deoxyuridine; D008727:Methotrexate