小白菊内酯对白血病干细胞增殖和细胞周期的调节作用及分子机制探究

Regulatory effect of parthenolide on proliferation and cell cycle of leukemia stem cells

目的:研究小白菊内酯对白血病干细胞增殖和细胞周期的调节作用及可能分子机制。方法:培养白血病干细胞,用不同浓度的小白菊内酯处理后检测细胞活力、细胞周期以及相关基因的mRNA含量。结果:(1)细胞活力和周期:小白菊内酯能够剂量依赖性地降低白血病干细胞的MTT值,20μmol/L小白菊内酯能够增加G2/M期的细胞比例,减少G0/G1期和S期细胞比例;(2)增殖和细胞周期调节基因:小白菊内酯能够剂量依赖性地降低c-myc、bcl-2、cyclinA1、cyclinE的mRNA含量;(3)信号通路:小白菊内酯能够剂量依赖性地降低基质细胞衍生因子1(SDF-1)及配体趋化因子受体CXCR4的mRNA含量。结论:小白菊内酯能够抑制白血病干细胞的增殖过程并使细胞周期停滞于G2期,可能的分子机制是抑制c-myc、bcl-2、cyclinA1、cyclinE表达以及SDF-1-CXCR4信号通路。

Objective： To study the regulatory effect of parthenolide on proliferation and cell cycle of leukemia stem cells and its possible molecular mechanism. Methods.. Leukemia stem ceils were cultured and processed with different concentrations of parthenolide. Then cell viability, cell cycle and mRNA contents of related genes were detected. Results： Parthenolide could decrease MTT values of leukemia stem cells in a dose dependent manner. 20 μmol/L parthenolide could increase GB/M phase ratio and decrease G0/G1 phase and S phase ratios. Parthenolide could decrease mRNA contents of c-myc, bcl -2, cyclinAl and cyclinE in a dose dependent manner. Parthenolide could decrease mRNA contents of SDF-1 and CXCR4 in a dose dependent manner. Conclusion： Parthenolide can inhibit leukemia stem cells proliferation and maintain cell cycle in G2 phase; possible molecular mechanism is inhibiting c-myc, bcl-2, cyclinA1 and cyclinE expressions and SDF 1-CXCR4 signal pathway.