丹参酮ⅡA乳剂对NB4细胞的诱导分化与凋亡作用

Differentiation and apoptosis of human promyelocytic leukemia cells induced by Tanshinone Ⅱ A emulsion

目的探讨丹参酮ⅡA乳剂对人早幼粒细胞白血病NB4细胞的诱导分化与凋亡作用。方法将丹参酮ⅡA乳剂与NB4细胞在体外共同培养5天,观察细胞形态变化,检测药物作用前后细胞NBT还原能力,采用MTT比色法检测NB4细胞的生长抑制率,并用流式细胞术测定细胞增殖周期及CD33和CD11b的表达。结果 6μg/ml丹参酮ⅡA对NB4细胞的抑制作用明显,生长抑制率为(73.9±3.2)%;丹参酮ⅡA乳剂对NB4细胞生长有明显诱导分化作用,诱导分化率为(92.4±1.2)%;NBT还原能力增强;CD33表达下降,CD11b表达升高。流式细胞术分析表明,NB4细胞经丹参酮ⅡA乳剂作用后,S期细胞数显著降低。结论丹参酮ⅡA乳剂能抑制NB4细胞生长,诱导NB4细胞向终末分化;丹参酮ⅡA以乳剂形式给药对NB4细胞的诱导分化与凋亡作用显著优于文献报道常用的丹参酮ⅡA二甲基亚砜溶液。丹参酮ⅡA乳剂有望用于人早幼粒白血病的临床治疗。

Objective To investigate the differentiation and apoptosis of human promyelocytic leukemia cells induced by Tanshinone Ⅱ A emulsion.Methods In vitro incubation of human promyelocytic leukemia cells with Tanshinone Ⅱ A emulsion for 5 days,cell differentiation were observed by cytomorphology and NBT test.The inhibition ratio of human promyelocytic leukemia cells was assayed by MTT test.Cell generation cycle,CD33 and CD11b expressions were analyzed by flow cytometry.Results Tanshinone Ⅱ A emulsion at concentration of 6 μg/ml had significant inhibition on human promyelocytic leukemia cells with inhibition ratio as（73.9±3.2）%.Human promyelocytic leukemia cells were induced and differentiated by Tanshinone Ⅱ A emulsion with cell differentiation ratio as（92.4±1.2）%.The reducing power of NBT significantly increased.Expression of CD33 decreased and that of CD11b increased.Flow cytometry analysis showed that the ratio of human promyelocytic leukemia cells in S phase reduced.Conclusions This study demonstrates that Tanshinone Ⅱ A emulsion can inhibit and induce differentiation of NB4 cells in vitro.Compared with Tanshinone Ⅱ A DMSO solution,Tanshinone Ⅱ A emulsion shows more advantages on the inhibition and differentiation of human promyelocytic leukemia cells with better biocompatibility.Tanshinone Ⅱ A will be promising to treat promyelocytic leukemia.