中文摘要：

目的探讨Fbxw8对人前列腺癌DU145细胞增殖及对增殖相关基因cyclinA、cyclinB、CDK1、p21和p27表达的影响。方法RT-PCR和Westernblot法验证Fbxw8siRNAs的干扰效率；利用CCK-8检测法检测细胞的增殖能力；流式细胞仪检测细胞周期分布情况；Westernblot法检测细胞增殖相关蛋白CDKl、CDK2、cyclinA、cyclinB、P21、P27的表达。结果Fbxw8siRNAs显著下调DU145细胞中Fbxw8mRNA及蛋白水平的表达（P〈0．01）；Fbxw8siRNAs显著抑制DU145细胞增殖活力，其中72h抑制最明显（P〈0．05）；流式细胞术分析显示，Fbxw8siRNAs可阻滞细胞于G2／M期，G2／M期细胞百分数由15．32％（controlsiRNA）增加到29．03％（Fbxw8siRNA1）和28．39％（Fbxw8siRNA2）；Westernblot结果显示，Fbxw8siRNAs可促进周期蛋白依赖性激酶抑制剂p21、p27的表达，同时下调G2／M期调控蛋白CDKI、CDK2、cyclinA及cyclinB1的表达。结论靶向抑制DU145细胞中Fbxw8的表达可显著抑制细胞的增殖，使阻滞细胞于G2／M期，并且可能是通过下调CDK1、CDK2、cyclinA及cyclinB1的表达，上调P21、P27的表达实现的。

英文摘要：

Objective To investigate the effect of F-box and WD repeat domain containing 8 （Fbxw8） on cell proliferation and the expression levels of proliferation-related genes such as cyclinA, cyclinB, cdkl, edk2, p21 and p27 in human prostate cancer DU145 cells. Methods RT-PCR and Western blot were applied to evaluate the interference efficiency of Fbxw8 siR- NAs. The cell proliferation was assessed by CCK-8 assay. The cell cycle of DU-145 cells was determined by flow cytometry. The expression levels of CDK1, CDK2, cyclin A, cyclinB, P21 and P27 proteins were detected by Western blot. Results Fbxw8 siRNA significantly de- creased the mRNA and protein of Fbxw8 in DU145 cells（P 〈0. 01 ）. The proliferation of DU- 145 cells was obviously inhibited after Fbxw8 siRNA intervention, especially in 72 h （P 〈 0. 05 ）. Flow cytometry analysis showed that Fbxw8 siRNA caused cell cycle arrest in G2/Mphase and cell percent of G2/M phase increased from 15.32% （ control siRNA） to 29.03% （Fbxw8 siRNA 1 ） and 28.39% （Fbxw8 siRNA 2）. Westert blot showed that the levels of CDK1, CDK2, CyclinA and CyclinB expression were down-regulated whereas the levels of p21 and p27 were up-regulated. Conclnsion Targeted inhibition of Fbxw8 in DU145 cells can sig- nificantly inhibit cell proliferation and block cells in G2 / M phase, which may be achieved by decreasing the expressions of CDK1, CDK2, cyclin A and cyclin B1 and increasing the expres- sions of P21 and P27.