摘要
本研究观察多西他赛对白血病耐药细胞株HL-60/ADR诱导凋亡的作用并探讨其对P-gp、BCL-2、BAX蛋白表达的影响,为临床解决白血病耐药问题提供新的思路和理论依据。采用光学显微镜、透射电子显微镜观察细胞形态学改变,Annexin V FITC/PI双标记流式细胞术检测细胞凋亡比率,MTT法检测细胞增殖抑制率,免疫细胞化学染色及计算机图文分析系统检测P-gp、BCL-2、BAX蛋白的表达水平。结果表明:HL-60/ADR细胞高表达P-gp,各浓度组之间P-gp的表达量没有差别。多西他赛对HL-60/ADR细胞生长有明显的抑制作用,并具有浓度和时间依赖性(r=0.853,r=0.989)。多西他赛可以诱导HL-60/ADR细胞凋亡,凋亡率没有随浓度变化的趋势。多西他赛作用HL-60/ADR细胞使BCL-2蛋白表达下降,BAX蛋白表达上升。结论:多西他赛可以诱导HL-60/ADR细胞凋亡,使细胞BCL-2蛋白表达下降,BAX蛋白表达上升。
This study was aimed to investigate the effect of Docetaxel on drug-resistant leukemia cell line HL-60/ ADR and its influence on expression of P-pg, BCL-2 and BAX proteins so as to provide a new strategy and theoretical basis for clinical solution of leukemia drug-resistance. The morphological changes of HL-60/ADR were observed by light and transmission electron microscopes; the cell apoptosis was detected by flow cytometry with Annexin V FITC/PI double labeling; the expressions of P-gp, BCL-2 and BAX were determined by immunohistochemical technique and computer image analysis system. The results showed that the HL-60/ADR cells treated with Docetaxel displayed typical apoptotic morphological changes; the Docetaxel significantly inhibited the growth of HL-60/ADR cells in concentration- and time-dependent manners （ r = 0. 853, r = 0.989） and induced the apoptosis of HL-60/ADR cells, but apoptosis rate did not showed the increase trend along with concentration change of drug. The HL-60/ADR cells highly expressed P-gp, there were no significant differences between each groups; the expression of BCL-2 and BAX in HL-60/ADR cells decreased and increased respectively. It is concluded that the Docetaxel induces apoptosis of HL-60/ADR cells, decreases the expression of BCL-2 protein and increases the expression of BAX protein.
出处
《中国实验血液学杂志》
CAS
CSCD
2010年第2期311-316,共6页
Journal of Experimental Hematology
基金
西安交通大学医学院第一附属医院临床研究中心基金资助
编号:200803
