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目的研究丙戊酸钠(VPA)对急性髓系白血病细胞株HL-60细胞的增殖抑制及诱导凋亡作用,探讨其可能作用机制。方法采用CCK-8法检测细胞生长抑制率;经瑞氏-姬姆萨(Wright-Giemsa)染色,光镜下观察经VPA处理后细胞的形态学改变;应用流式细胞仪检测细细胞周期和细胞凋亡率。结果 VPA对HL-60细胞的增殖抑制作用呈时间和浓度依赖性。经2.0mmol/L VPA处理HL-60细胞48h后,显微镜下可见凋亡细胞胞体固缩、核固缩、核碎裂及凋亡小体。经1.0和2.0mmol/L VPA处理HL-60细胞48h后,流式细胞仪检查结果表明细胞凋亡率由处理前的(1.25±0.457)%分别上升为(3.27±0.984)%和(10.3±3.4)%,差异有统计学意义(P<0.05);G0/G1期细胞比例逐渐上升,S期细胞比例及细胞增殖指数(PI)呈下降趋势,细胞被阻滞在G0/G1期(P<0.01)。结论 VPA对HL-60细胞具有增殖抑制和诱导细胞凋亡作用,且呈剂量-时间依赖性;作用机制与细胞周期阻滞有关。
Objective To investigate the effects of VPA on the proliferation and apoptosis of acute myeloid leukemia HL-60 cells and to explore its possible mechanism. Methods The cell growth inhibition rate was determined by CCK-8 method. The morphological changes of cells treated with VPA were observed under light microscope by Wright-Giemsa staining. The cell cycle and Rate of apoptosis. Results VPA inhibited the proliferation of HL-60 cells in a time and concentration-dependent manner. The HL-60 cells were treated with 2.0mmol / L VPA for 48h, and the apoptotic cells were observed under a microscope to observe the cell shrinkage, nuclear pyknosis, nuclear fragmentation and apoptotic bodies. The results of flow cytometry showed that the apoptotic rate of HL-60 cells increased from (1.25 ± 0.457)% before treatment to (3.27 ± 0.984)% and (10.3 ± (P <0.05). The proportion of cells in G0 / G1 phase increased gradually while the proportion of cells in S phase and PI decreased. The number of cells arrested in G0 / G1 phase (P <0.01). Conclusion VPA can inhibit proliferation and induce apoptosis of HL-60 cells in a dose-time-dependent manner. The mechanism of action is related to cell cycle arrest.