摘要
目的观察携带NDRG2基因的腺病毒（Ad．NDRG2）与多西紫杉醇（DT）联合给药对人前列腺癌细胞株DUl45的抗肿瘤增效作用。方法以Ad．NDRG2感染体外培养的DUl45细胞，采用Western—blot方法检测CyclinDl、CyclinE、NDRG2蛋白表达水平的变化。流式细胞仪检测和MTT试验分析Ad-NDRG2给药后DUl45细胞对DT敏感性的变化。建立裸鼠移植瘤模型，观察Ad—NDRG2与DT联合给药的体内抗肿瘤作用。结果Ad-NDRG2感染后，DUl45细胞中NDRG2表达明显增加，而CyclinDl和CyclinE表达水平降低。Ad—NDRG2协同10。mo]／L以上浓度DT作用48h，可增强对DUl45细胞的生长抑制作用（抑制率：41．8％，t=4．18，P〈0．01），增强诱导凋亡作用（凋亡率=32．4％，）（2=11．66，P〈0．05），并且使DT所致的G2／M期细胞比例由50．2％变为23．6％，部分逆转了其G2／M期阻滞。动物实验表明：DT组、Ad．NDRG2组、Ad．NDRG2与DT联合给药组其移植瘤的抑瘤率分别为30．7％、28．2％和55．8％，两药相互作用指数（CDI）为0．89。结论腺病毒介导NDRG2基因感染细胞后，增加了人前列腺癌DUl45细胞在体内及体外对多西紫杉醇的敏感性。
Objective To investigate the antitumor activities of adenovirus-mediated NDRG2 gene （Ad-NDRG2） and docetaxel on human prostate cancer DU145 cells. Methods The protein expressions of cyclin D1 ,cyclin E, and NDRG2 in the cells were determined by Western blot. MTY and flow cytometry were used to observe the effects of docetaxel （10-6 mol/L, 10-7 mol/L, and 10-s mol/L） and Ad-NDRG2 on prostate cancer cell line DU145 in single or synergistic administration ways for 24 and 48 hours in vitro. Male BALB/C-nu mice with DU145 prostate cancer cell lines were treated by docetaxel and Ad-NDRG2 singly or synergistically in vivo. Results After infected by adenovirus, the protein expression of NDRG2 increased, but cyclin D1 and cyclin E decreased in DU145 cells. Ad-NDRG2 inhibited the cell growth （inhibition ratio = 41.8%, t = 4. 18, P 〈 0. 01 ）, promoted apoptosis （ apoptosis ratio = 32. 4%, G2 = 11.66, P 〈 0. 05）, changed the ratio of G2/M phase from 50. 2% to 23.6%, and reversed partially the G：/M arrest, of DU145 cells induced by 10-7 mol/L docetaxel. In vivo experiment showed that docetaxel, Ad-NDRG2, and combination of docetaxel and Ad-NDRG2 inhibited tumor growth with a inhibition rate of 30. 7% ,28.2%, and55.8% ,respectively. The coefficient of drug interaction （CDI） of docetaxel and Ad-NDRG2 was 0. 89. Conclusions Ad-NDRG2 can enhance the growth suppression and apoptosis induced by docetaxel in synergistic way in vitro and in vivo. It demonstrated the great potential of Ad-NDRG2 in the treatment of androgen-independent prostate carcinoma.
出处
《中国医师杂志》
CAS
2012年第11期1455-1458,共4页
Journal of Chinese Physician
基金
国家自然科学基金资助项目（30830054）
