Benzylacyclouridine enhances 5-fluorouracil cytotoxicity against human prostate cancer cell lines

被引：8

作者：

Yee, LK

Chu, E

Pan, BC

Chu, SH

Chen, TM

Lipsky, MH

Chu, MYW ^{[1
]}

Calabresi, P

机构：

[1] Brown Univ, Dept Med & Clin Pharmacol, Providence, RI 02903 USA

[2] Rhode Isl Hosp, Providence, RI 02903 USA

[3] Yale Univ, Sch Med, Yale Canc Ctr, Dept Med, W Haven, CT USA

[4] Yale Univ, Sch Med, Yale Canc Ctr, Dept Med & Pharmacol, W Haven, CT USA

[5] VA Connecticut Healthcare Syst, W Haven, CT USA

来源：

PHARMACOLOGY | 1998年 / 56卷 / 02期

关键词：

benzylacyclouridine; 5-fluorouracil; uridine phosphorylase; prostate cancer;

D O I：

10.1159/000028185

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：80 / 91

页数：12

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