摘要
目的 研究丹参酮 A(Tanshinone A,Tan A)联合全反式维甲酸 (ATRA)对早幼粒细胞白血病细胞 (NB4 )诱导分化及凋亡的协同效应。方法 0 .5 μg/ m l Tan A分别联合 0 .5 μg/ ml、0 .2 5 μg/ ml和 0 .12 5 μg/ml ATRA作用 NB4细胞 5 d,观察 NB4细胞形态学变化 ,检测硝基蓝四氮唑 (NBT)还原能力 ;流式细胞术检测CD11b,CD33的表达 ,并进行细胞周期和细胞凋亡分析。结果 Tan A联合 ATRA可协同诱导 NB4细胞分化和凋亡。联合作用组第 5 d细胞生长抑制率均超过 80 % ;90 %左右的 NB4细胞分化 ,其中杆状和分叶核细胞比例超过6 5 % ;NBT还原能力显著升高。流式细胞术分析显示 CD11b表达升高 ,CD33表达降低 ;G0 / G1 期细胞增加 ,有明显的细胞凋亡 ,与 Tan A或 ATRA单独作用组相比均有显著性差异 (P<0 .0 1)。Tan A与 ATRA(0 .12 5 μg/ m l～0 .5 μg/ m l)联合对 NB4细胞的影响没有明显的浓度依赖倾向。结论 Tan A联合 ATRA对 NB4细胞诱导分化和凋亡有协同作用 ;在 ATRA一定浓度范围内 ,这种协同作用无 ATRA剂量依赖性。
Objective To evalutate the synergistic effects of Tanshinone ⅡA combined with all-trans retinoic acid(ATRA) on the differentiation and apoptosis of human acute promyelocytic leukemia(APL) cell line(NB4). Methods The NB4 cells were treated with 0.5 μg/ml TanshinoneⅡA combined with 0.5 μg/ml,0.25 μg/ml and 0.125 μg/ml ATRA respectively in culture. Cells differentiation was demonstrated by morphology and NBT reduction assay. The expression of CD11b and CD33, cell cycle and apoptosis induced by these drugs were measured by flow cytometry (FCM). Results The proliferative inhibition rate of the combination of TanⅡA with ATRA was much higher. The differentiated cells accounted for over 90 percent, among them the band forms and neutrophils constituted more than 65 percent. NBT reduction and CD11b expression were much higher, and expression of CD33 was lower than that of TanⅡA or ATRA alone(P<0.01). FCM analysis also showed that combination of TanⅡA with ATRA arrested NB4 cells in G 0/G 1 phase and induced significantly apoptosis of NB4 cells (P<0.01). There were no significant dose dependent effects induced by ATRA in combination with TanⅡA at 0.125 μg/ml to 0.5 μg/ml on differentiation and apoptosis of NB4 cells. Conclusion The combination of TanⅡA with ATRA has synergistic effects on differentiation and apoptosis of NB4 cells. The effects do not increase with the dosage escalation of ATRA.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2004年第6期788-791,共4页
Journal of Sichuan University(Medical Sciences)
基金
四川省科技厅科研基金 ( 2 0 0 0 -15 1)资助
