中文摘要：

目的：探讨细胞周期蛋白激酶抑制剂（nav叩irid01）在体内外抑制尤文肉瘤阿霉素耐药细胞株WE-68／ADR增殖的作用及其机制。方法：四甲基偶氮唑蓝法（MTF法）测定细胞增殖抑制率。流式细胞计数法测量flavopirid。1给药后WE-68／ADR细胞周期的变化及凋亡率。免疫印迹法（western-blot）检测细胞中Bax、Bcl-2、p53及活化型多聚ADP核糖多聚酶（PARP-85）蛋白的表达。皮下注射WE-68／ADR细胞建立荷瘤裸鼠模型，17flavopiridol腹腔内给药，测量肿瘤体积及裸鼠体重变化，计算肿瘤抑制率。结果：Flavopiridol可抑制尤文肉瘤阿霉素耐药细胞株WE-68／ADR的细胞增殖，其效果呈时间及浓度相关性（P〈0．05）。Flavopiridol给药后，耐药细胞株WE-68／ADR的细胞凋亡比明显高于对照组（P〈0．05）。同时，耐药细胞株中的Bax、p53及PARP-85的表达增加，而Bcl-2的表达被下调。Flavopifidol可有效抑制荷瘤小鼠体内耐药细胞株的生长。结论：细胞周期蛋白激酶抑制剂flavopiridol可在体内外有效抑制尤文肉瘤阿霉素耐药细胞株的增殖，其机制可能与p53介导的线粒体凋亡信号传导途径有关。

英文摘要：

Objective ：To investigate the inhibitory effect of cyclin- dependent kinase inhibitor （flavopiridol） on the proliferation of adriamycin - resistant Ewing~ sarcoma cells, WE - 68/ADR and its underlying mechanism in vitro and in vivo. Methods ：The proliferation of WE - 68/ADR cells was determined by using MTr method. Cell cycle progres- sion and apoptosis ratio were determined by flow cytometry. The expression of Bax,p53, bcl - 2, cleaved - PARP were de- tected by western blot. The xenograft model was successfully established via injecting WE - 68/ADR cells subcutane- ously in nude mice. Mice were monitored for changes in the tumor volume：and body weight after flavopifidol was injec- ted intraperitoneally, Results：After exposure to flavopiridol,the growth of WE -68/ADR cells was inhibited in a time - and dose - dependent manner （ P 〈 0.05 ）. Apoptosis rate of WE - 68/ADR was higher than that of control group （ P 〈 0.05 ）. The expression of bcl - 2 was down - regulated, and the expression of p53, Bax and cleaved - PARP were up - regulated. The inhibitory effect of flavopiridol on ADR clones of Ewing＇s sarcoma in the treatment group was ob- served compared with the control group in vivo. Conclusion ： Flavopiridol can inhibit the growth of drug - resistant EFTs cells in vitro and in vivo ,which might be mediated by p53 -dependent mitochondrial apoptosis pathway.