Sequence-dependent antagonism between tamoxifen and methotrexate in human breast cancer cells

High-dose methotrexate (MTX) cytotoxicity is decreased in MCF-7 breast cancer cells when the chemoendocrine agent tamoxifen (TAM) is given to cells 24 hours prior to MTX (early TAM). However; when breast cancer cells are exposed to TAM 24 hours after MTX (delayed TAM), MTX cytotoxicity is enhanced by TAM. The growth of cells exposed to 10 mu M TAM and 10 mu M MIX alone ol in combination with early TAM plus MTX had the following order: TAM > TAM (early) + MTX > MTX. The percentages of control rates for TAM, MTX, and TRM (early) + MTX are 74.71 +/- 1.36 %, 22.13 +/- 2.76%, and 38.17 +/- 2.75 %, respectively. The inhibitory sequence fi om cells exposed to MTX + TAM (delayed TAM), MTX and TAM alone is MTX + TAM (delayed TAM) > MTX > TAM; and the percentages of control rates were 16.87 87 % (MTX + TAM [delayed TAM]), 25.92 +/- 2.14 % (MTX), and 54.08 +/- 14.79 % (TAM). These studies suggest chat: (a) the interactions between TAM and MTX ale sequence-dependent; (b) TAM antagonizes the effect of MTX when TAM administration precedes MTX; and (c) TAM enhances the effect of MTX when TAM administration follows MTX.