摘要
目的研究丹参酮ⅡA(TanⅡA)与三氧化二砷(ATO)联合对急性早幼粒白血病细胞(NB4)分化以及凋亡有无协同作用。方法用TanⅡA联合ATO作用于NB4细胞。观察药物作用不同时间段的活细胞数,计算实验各时段的生长抑制率;Giemsa染色与透射电镜观察细胞形态学变化;流式细胞术Annexin V法测定细胞凋亡率,并进行细胞周期和细胞凋亡分析。结果①TanⅡA与ATO联合对NB4细胞生长有协同抑制作用,这种抑制作用随作用时间及联合ATO浓度的增加而增加。1.0μg/mL TanⅡA分别与0.125、0.25以及0.5μmol/LATO联合作用5 d对NB4细胞的生长抑制率均强于相应浓度ATO单独作用对NB4细胞的生长抑制率(P<0.01);②TanⅡA与ATO联合对诱导NB4细胞凋亡有协同作用。1.0μg/mL TanⅡA分别与0.5μmol/L和1.0μmol/L ATO联合作用NB4细胞1 d,NB4细胞的凋亡率分别比相应ATO单独用药组的促凋亡效应增强(P<0.05),TanⅡA与0.5μmol/L ATO联合的促凋亡协同效应持续3 d;③TanⅡA与ATO联合对NB4细胞增殖有协同抑制作用,使G0/G1期细胞增多,S期细胞减少。1.0μg/mL TanⅡA分别与0.125、0.25和0.5μmol/L ATO联合作用NB4细胞3 d的增殖指数(PI)均低于相应单药的PI值(P<0.05)。结论TanⅡA联合ATO对诱导NB4细胞凋亡有明显的协同作用,这种协同作用和联合使用的ATO的浓度密切相关;TanⅡA联合ATO对NB4细胞诱导分化未显示明显的协同作用。
Objective To evaluate the synergistic effects of Tanshinone 1] A（Tan Ⅱ A）eombined with arsenic trioxide（ATO） on apoptosis and differentiation of NB4 cells. Methods The NB4 cells were treated with Tan Ⅱ A, ATO, and Tan Ⅱ A combined with ATO, respectively. The proliferative inhibition rates of NB4 cells induce by Tan Ⅱ A, ATO and their combination were calculated on the fifth day. The morphology of cell differentiation was observed by Giemsa stain and transmission electron microscope（TEM）. The cell cycle, proliferation index and apoptosis induced by these drugs were measured by flow cytometry（FCM）. Results （I） Combination treatment of TanⅡ A with ATO had synergistic effects on the proliferative inhibition of NB4 cells. This synergistic effects showed a dose and time-dependent manner. The proliferative inhibition rates of NB4 cells were increased gradually after the treatment of 1.0 μg/mL Tan Ⅱ A combination with 0. 125μmol/L, 0. 25μmol/L and 0. 5μmol/L ATO respectively,which was much higher than those treated by corresponding ATO alone（P〈0. 01）;（1）Combination treatment of Tan Ⅱ A with ATO had synergistic effects on the apoptosis of NB4 cells. The synergistic effects of 1.0 μg/mL Tan Ⅱ A combined with 0.5 μmol/L ATO on the apoptosis of NB4 cells lasted for 3 days;（3）Combination treatment of TanⅡ A with ATO had synergistic inhibition effects on proliferation of NB4 cells, which decreased the number of cells in S phase and increased cells in G0/G1 phase. The proliferation indicies（PI） of NB4 cells treated with the combination of Tan Ⅱ A and different level of ATO were lower than those treated by corresponding ATO alone（P〈0. 05）. Combination treatment of Tan Ⅱ A with ATO had no significant synergistic effects on the differentiation of NB4 cells. Conclusion Combination treatment of Tan Ⅱ A with ATO has significant synergistic effects on the apoptosis of NB4 cells. This synergistic effects is related to the dosage and treatment time. The significa
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2010年第1期57-61,共5页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金(批准号30470748)资助
