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标题：2′-Deoxycytidine Decreases the Anti-tumor Effects of 5-Fluorouracil on Mouse Myeloma Cells
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作者：Ayano Iwazaki ; Masanori Yoshioka
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：6
页码：1024-1027
DOI：10.1248/bpb.33.1024
出版社：The Pharmaceutical Society of Japan
摘要：2′-Deoxycytidine (dCyd), a pyrimidine nucleoside found at high concentrations in the plasma of cancer patients with a poor prognosis after chemotherapy, is considered to be a biomarker for breast cancer. 5-Fluorouracil (5FU) is a nucleoside analog and is used as an anti-tumor agent in patients whose plasma dCyd concentrations are increased. Because both dCyd and 5FU are pyrimidine analogues, it is possible that they have pharmacokinetic/ pharmacodynamic interaction, by which the anti-cancer efficacy of 5FU would be reduced. Here, we examined the effects of dCyd on the cytotoxicity of 5FU on mouse myeloma SP2/0-Ag14 (SP2/0) cells lacking hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) and RH4 hybridomas with HGPRT under asynchronized conditions. The reduced cell viability by 5FU was restored by co-, but not pre-, treatment of dCyd in both SP2/0 and RH4 cells, but this effect in the former tended to be greater than that in the latter, suggesting a possible involvement of HGPRT in the interaction, although this might not be a major mechanism. Moreover, dCyd administration to SP2/0 myeloma-bearing mice tended to shorten their 5FU-induced prolonged survival in vivo . Collectively, these results indicate that dCyd decreases the anti-tumor efficacy of 5FU and that a metabolic pathway via HGPRT is involved partially in this interaction. The evaluation of dCyd as a biomarker is believed to provide valuable information for effective and safe chemotherapy with 5FU.
关键词：2′-deoxycytidine;5-fluorouracil;biomarker;hypoxanthine-guanine-phosphoribosyl transferase;cell viability;survival