Moscow J A
Department of Pediatrics, University of Kentucky Medical Center, Lexington 40536, USA.
Leuk Lymphoma. 1998 Jul;30(3-4):215-24. doi: 10.3109/10428199809057535.
Methotrexate (MTX), the antifolate drug widely used as both an anticancer chemotherapeutic drug and as an immunosuppressive agent, mimics natural folates to inhibit critical cellular biosynthetic pathways. One of the most important determinants of cellular sensitivity to MTX is the degree to which this drug is internalized by cancer cells, and one of the major pathways of folate uptake results from the activity of the reduced folate carrier (RFC). Decreased RFC activity has been associated with several models of transport-mediated MTX resistance. Recently, the rodent and human genes which encode this protein have been isolated (RFC1), and defects in the expression of RFC1 genes have been identified in transport-deficient, MTX-resistant cell lines. Therefore, these studies have demonstrated the importance of RFC1 expression in transport-mediated antifolate drug resistance. In addition, however, studies of both MTX uptake in cancer cells and of folate transport in physiologic systems indicate that there are other proteins with uptake characteristics similar to RFC, and which maybe encoded by genes other than RFC1.
甲氨蝶呤（MTX）是一种广泛用作抗癌化疗药物和免疫抑制剂的抗叶酸药物，它模拟天然叶酸来抑制关键的细胞生物合成途径。细胞对MTX敏感性的最重要决定因素之一是癌细胞摄取这种药物的程度，而叶酸摄取的主要途径之一是由还原型叶酸载体（RFC）的活性导致的。RFC活性降低与几种转运介导的MTX耐药模型有关。最近，编码该蛋白的啮齿动物和人类基因已被分离出来（RFC1），并且在转运缺陷的MTX耐药细胞系中已鉴定出RFC1基因表达的缺陷。因此，这些研究证明了RFC1表达在转运介导的抗叶酸药物耐药性中的重要性。然而，此外，对癌细胞中MTX摄取和生理系统中叶酸转运的研究表明，还有其他具有与RFC相似摄取特征的蛋白质，并且它们可能由RFC1以外的基因编码。
