文章基本信息

标题：Inhibition of Doxorubicin-Induced Cell Death in Vitro and in Vivo by Cycloheximide
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作者：Shinobu FURUSAWA ; Shinya NAKANO ; Kaori KOSAKA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1995
卷号：18
期号：10
页码：1367-1372
DOI：10.1248/bpb.18.1367
出版社：The Pharmaceutical Society of Japan
摘要：We studied the effects of the protein synthesis inhibitor, cycloheximide (CH), on cell killing by doxorubicin (DOX) in vitro and in vivo. At the concentration of CH used (1μg/ml) the cytotoxicity of DOX was reduced in cultured P388 leukemia cells. An analysis of the DNA histogram obtained by flow cytometry showed that DOX exerts its growth-inhibitory effect by blocking the cell cycle at the G₂/M phase in P388 cells. Treatment with CH diminished this blocking effect. When CH was added to the growth medium before DOX exposure, no change in intracellular DOX accumulation was observed. Treatment with CH (15mg/kg) significantly diminished the lethality of DOX (20mg/kg) in mice and it also reduced the antitumor activity of mice with P388 leukemia. Thus, CH inhibited cell death induced by DOX in vitro and in vivo. These results suggest that CH has an antagonistic effect on the pharmacological actions of DOX in cells and mice. The cytoprotective effect of CH may be due to protein synthesis inhibition.
关键词：doxorubicin;cell death;cycloheximide;cytotoxicity;antitumor activity