SYNERGISTIC ACTION OF TIAZOFURIN AND DIFLUORODEOXYCYTIDINE ON DIFFERENTIATION AND CYTOTOXICITY

被引:13
作者
BAN, J
WEBER, G
机构
[1] INDIANA UNIV, SCH MED, EXPTL ONCOL LAB, INDIANAPOLIS, IN 46202 USA
[2] CENT INST TUMORS, YU-41000 ZAGREB, CROATIA
关键词
D O I
10.1016/0006-291X(92)90625-U
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tiazofurin (TR), an inhibitor of IMP dehydrogenase, causes remissions and induced differentiation in human leukemia through lowering the concentrations of GTP and dGTP. A deoxycytidine analog, difluorodeoxycytidine (DFDC), is an anti-tumor agent phosphorylated by deoxycytidine kinase, resulting in decreased concentration of dCTP, leading to inhibition of DNA synthesis. In HL-60 cells DFDC induced differentiation and inhibited proliferation in a dose-dependent manner (IC50 = 4 nM); TR provided synergism with DFDC. DFDC inhibited proliferation in OVCAR-5 human ovarian carcinoma cells (IC50 = 25 nM) and colony formation in PANC-1 human pancreatic carcinoma cells (IC50 = 2 nM) and rat hepatoma 3924A cells (IC50 = 22 nM). TR and DFDC are synergistically cytotoxic in hepatoma cells and additive in PANC-1 cells. The two drugs together should be helpful in treating leukemias and solid tumors in humans. © 1992.
引用
收藏
页码:551 / 559
页数:9
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