Bowen D, Southerland W M, Hawkins M, Johnson D H
Department of Pharmacology, Howard University College of Medicine, Washington, D.C. 20059, USA.
Anticancer Res. 2000 May-Jun;20(3A):1415-7.
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 microM TAM and 10 microM MTX alone or 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 TAM (early) + MTX are 74.71 +/- 1.36%, 22.13 +/- 2.76%, and 38.17 +/- 2.75%, respectively. The inhibitory sequence from 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 that: (a) the interactions between TAM and MTX are 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.
当在甲氨蝶呤（MTX）给药前24小时给予化学内分泌药物他莫昔芬（TAM）（早期TAM）时，MCF - 7乳腺癌细胞中的高剂量甲氨蝶呤（MTX）细胞毒性降低。然而，当乳腺癌细胞在MTX给药后24小时暴露于TAM（延迟TAM）时，TAM会增强MTX的细胞毒性。单独暴露于10微摩尔TAM和10微摩尔MTX或与早期TAM加MTX联合的细胞生长情况如下：TAM > TAM（早期）+ MTX > MTX。TAM、MTX以及TAM（早期）+ MTX的对照率百分比分别为74.71±1.36%、22.13±2.76%和38.17±2.75%。暴露于MTX + TAM（延迟TAM）、单独的MTX和TAM的细胞的抑制顺序为MTX + TAM（延迟TAM）> MTX > TAM；对照率百分比分别为16.87%（MTX + TAM [延迟TAM]）、25.92±2.14%（MTX）和54.08±14.79%（TAM）。这些研究表明：（a）TAM与MTX之间的相互作用取决于给药顺序；（b）当TAM给药先于MTX时，TAM拮抗MTX的作用；（c）当TAM给药在MTX之后时，TAM增强MTX的作用。
