中文摘要：

目的探讨2-脱氧-D-葡萄糖（2-DG）对多西紫杉醇（Doc）诱导雄激素非依赖型前列腺癌PC3和DU145细胞凋亡的增敏作用及其可能的机制。方法采用MTr法检测Doe与2-DG单用或合用对细胞增殖的抑制作用，计算q值反映联合用药效果；流式细胞技术（FCM）检测细胞凋亡率；ATP检测试剂盒检测细胞内ATP含量的变化；免疫印迹Western印迹技术检测泛素蛋白酶体系统（UPS）功能的内源性蛋白ubiquitinatedprotein（Ub）、hspT0的表达。结果2-DG能抑制PC3及DU145细胞的增殖，呈剂量、时间依赖性，但诱导凋亡作用不明显；Doc0．1、0．5、2．5nmolfL对PC3细胞及DU145细胞作用48h的增殖抑制率分别为10．71％、25．32％、56．46％及12．28％、23．94％、63．43％。联用2-DG1．0g／L后增殖抑制率为：27．15％、58．74％、87．95％及29．53％、59．41％、90．48％，Doc与2-DG联用后可明显增加其抑制率，两药有协同作用（q值均〉1．15）；Doc0．5nmol／L与2-DG1．0g／L联合作用PC3细胞及DUl45细胞48h的凋亡率为：46．49％及53．64％，明显高于Doc0．5nmol／L单独作用的凋亡率：21．30％及18．92％（均P〈0．05）；2-DG1．0g／L分别作用PC3和DU145细胞0、12、24、48、72h后，ATP检测试剂盒测ATP相对浓度为13．75、11．23、10．19、9．81、9．02和15．00、12．59、11．38、10．54、10．37；同时Western印迹检测发现ub及HspTO蛋白出现聚集。结论2-DG可增强雄激素非依赖型前列腺癌细胞对Doc化疗的敏感性；其机制可能与下调细胞内ATP浓度导致蛋白酶体功能抑制有关。

英文摘要：

Objective To explore the antitumor effects of 2-deoxyglucose （2-DG） plus docetaxel （Doe） on PC3 and DU145 cells and its mechanism. Methods The proliferation of cells was detected by methyl thiazolyl tetrazolium （MTI＇） assay. Then propidium iodide （PI） staining measured apoptotic cells on flow cytometry. ATP assay kit was used to detect ATP content. The expressions of proteins ubiquitinated protein （Ub） and Hsp70 were measured by Western blot. Results 2-DG could inhibit proliferation of PC3 and DU145 cells in a dose- and time-dependent manner. However, it could not induce apoptosis in PC3 or DU145. The inhibition rates for PC3 proliferation at 48 h by Doc with concentrations of 0. 1, 0. 5, 2. 5 nmol/L were 10. 71% , 25.32% and 56. 46% respectively. The inhibition rates for DU145 cell proliferation at 48h by Doc with concentrations of 0. 1, 0. 5, 2. 5 nmo]./L were 12. 28% , 23.94% and 63.43% respectively. The inhibition rates for PC3 cell proliferation by Doe plus 2-DG with a concentration of 1.0 g/L were 27.15% , 58. 74% and 87.95% respectively and 29. 53% , 59.41%, and 90.48% for DU145 respectively. 2-DG could enhance the effectiveness of inhibition to PC3 and DU145 proliferation by Doc with a synergistic manner （ all q 〉 1.15 ）. The apoptotic rates for PC3 and DU145 induced by Doe 0. 5 nmol/L plus 2-DG 1.0 g/L at 48 h were 46.49% and 53.64% respectively. The apoptotic rates were significantlyhigher than Doc 0. 5 nmol/L alone （21.30% for PC3 and 18.92% for DU145 respectively） （P 〈0. 05）. The ATP relative concentration for PC3 in 2-DG 1.0 g/L at 0, 12, 24, 48, and 72 h were 13.75, 11.23, 10.19, 9.81 and 9.02 and for DU145 15.00, 12.59, 11.38, 10.54 and 10.37 respectively. Simultaneously, Western blot showed that Ub and Hsp70 protein were expressed intensively. Conclusions 2-DG can enhance the sensitivity of androgen-independent prostate cancer cells to docetaxel. Its mechanism may be associated with the decrease of proteasome function.