Yee L K, Chu E, Pan B C, Chu S H, Chen T M, Lipsky M H, Chu M Y, Calabresi P
Department of Medicine and Clinical Pharmacology, Brown University, Rhode Island Hospital, Providence 02903, USA.
Pharmacology. 1998 Feb;56(2):80-91. doi: 10.1159/000028185.
At a nontoxic growth inhibitory concentration benzyloxyacyclouridine (BAU), a potent and specific inhibitor of uridine phosphorylase (UrdPase), enhanced 5-fluorouracil (5-FU) cytotoxic activity against human prostate cancer PC-3 and DU-145 cell lines. The BAU/5-FU combination exhibited greater antitumor activity in vivo using PC-3 human xenografts compared to 5-FU alone, with no associated increase in animal host toxicity. The mechanism(s) responsible for the enhanced in vitro and in vivo activity of this combination may involve enhanced formation of the 5-FU nucleotide metabolites FdUMP, FdUTP, and FUTP resulting in enhanced inhibition of thymidylate synthase (TS) and increased incorporation of fluoropyrimidine metabolites into tumoral RNA and DNA.
在无毒生长抑制浓度下，苄氧基阿糖胞苷（BAU）是一种有效的尿苷磷酸化酶（UrdPase）特异性抑制剂，可增强5-氟尿嘧啶（5-FU）对人前列腺癌PC-3和DU-145细胞系的细胞毒性活性。与单独使用5-FU相比，BAU/5-FU组合在使用PC-3人异种移植瘤的体内实验中表现出更大的抗肿瘤活性，且动物宿主毒性没有相应增加。这种组合在体外和体内活性增强的机制可能涉及5-FU核苷酸代谢产物FdUMP、FdUTP和FUTP的形成增加，从而增强对胸苷酸合成酶（TS）的抑制，并增加氟嘧啶代谢产物掺入肿瘤RNA和DNA。
