Kennedy D G, Van den Berg H W, Clarke R, Murphy R F
Biochem Pharmacol. 1985 Aug 15;34(16):2897-903. doi: 10.1016/0006-2952(85)90013-9.
The modulating effects of leucovorin on the synthesis of methotrexate (MTX) polyglutamates in the MCF-7 human breast cancer cell line have been investigated using a paired-ion high performance liquid chromatography (HPLC) system. Leucovorin decreased the intracellular level of MTX and profoundly affected polyglutamate synthesis irrespective of whether it was administered with or after MTX. Inhibition of MTX polyglutamate synthesis was also observed when concentrations of leucovorin too low to affect intracellular levels of MTX were employed. Leucovorin did not promote efflux of MTX from the MCF-7 cells and did not affect the distribution of the retained drug amongst the various polyglutamate forms.
使用配对离子高效液相色谱（HPLC）系统研究了亚叶酸对MCF-7人乳腺癌细胞系中甲氨蝶呤（MTX）多聚谷氨酸合成的调节作用。无论亚叶酸是与MTX同时给药还是在MTX给药后给药，亚叶酸均可降低MTX的细胞内水平，并对多聚谷氨酸的合成产生深远影响。当使用浓度过低而无法影响MTX细胞内水平的亚叶酸时，也观察到MTX多聚谷氨酸合成受到抑制。亚叶酸不会促进MTX从MCF-7细胞中流出，也不会影响保留药物在各种多聚谷氨酸形式之间的分布。
