丹参酮ⅡA诱导原代培养人急性早幼粒细胞白血病细胞分化

Terminal Differentiation of Human Acute Promyelocytic Leukemia (APL) Cells Induced by Tanshinone Ⅱ A in Primary Culture

为探讨丹参酮ⅡA（tanshinoneⅡA，TanⅡA）对原代培养的人急性早幼粒细胞白血病（APL）细胞的诱导分化作用，将5例APL患者白血病细胞分别与0．5μg／mlTanⅡA在体外共同培养7天，而后观察细胞形态变化，并测定药物作用前后细胞的四唑氮蓝（NBT）还原能力，用流式细胞术测定细胞DNA周期、CD33及CD11b的表达。结果显示：0．5μg／mlTanⅡA可诱导82．5％±4．8％的APL细胞向终末细胞分化，并使细胞生长明显受抑，NBT还原能力显著增强；CD33表达下降，CD11b表达升高，与全反式维甲酸的作用无显著性差异（P＞0．05）。流式细胞术分析显示，TanⅡA将APL细胞阻滞于G0／G1期，S期细胞数明显减少。本研究结果表明，TanⅡA在体外能诱导APL细胞向终末分化，其作用与全反式维甲酸相当，进一步开发它将具有一定的临床价值。

The aim of this study was to investigate whether Tanshinone I A (Tan I A) can induce human actute promyelocytic leukemia (APL) cells to differentiate or not in primary culture. The APL cells from 5 cases were cultured respectively with Tan I A at the concentration of 0. 5μg/ml for 7 days in vitro. The differentiations of these leukemia cells were observed cytomorphologically and examined by nitroblue tetrazolium (NBT) test. The cell DNA cycle and mernbrane cluster differentiation (CD) antigens (CD33, CD11b) were analyzed by flow cytometry. The results showed that 82. 5%± 4. 8% of APL cells were induced into morphologically and functionally differentiated cells. The cell growth curve showed that the growth of APL cells was inhibited. The degree of differentiation and growth inhibition induced by Tan I A was not different from that by ATRA(P>0.05). Flow cytometry analysis showed that Tan I A arrested APL cells in G0/G1 phase and inhibited cellularDNA synthesis. This study demonstrates that Tan I A can induce differentiation of APL cells in vitro, and hence it is worthy of further studies for clinical use.