桂皮醛体外诱导慢性髓系白血病细胞凋亡的机理研究

Mechanism of Cinnamic Aldehyde-inducing Apoptosis of Chronic Myeloid Leukemic Cells In Vitro

本研究探讨桂皮醛(cinnamic aldehyde,CA)对慢性髓系白血病(chronic myeloid leukemia,CML)细胞的诱导凋亡作用及其机制。以不同浓度的桂皮醛作用于体外培养的K562细胞和骨髓CML原代细胞,流式细胞术检测细胞凋亡率,Real-time PCR技术检测K562细胞BCR-ABL融合基因表达变化,免疫印迹法检测K562细胞CrkL磷酸化水平和C-MYC蛋白表达。结果表明:桂皮醛可诱导K562和骨髓CML原代细胞凋亡。在K562细胞凋亡过程中,BCR-ABL融合基因mRNA的表达、CrkL蛋白磷酸化及C-MYC蛋白表达均明显受抑。结论 :桂皮醛体外诱导CML细胞凋亡,其机制与BCR-ABL融合基因表达和功能受抑有关。

The aim of this study was to investigate the apoptosis-inducing effect of cinnamic aldehyde （CA） on chronic myeloid leukemic （CML） cells and its mechanism. K562 cells and primary bone marrow mononuclear cells （MNC） from patients with CML were treated by various concentrations of CA. Flow cytometry was employed to measure the apoptosis of K562 cells and primary CML bone marrow MNC. Western blot was used to determine the expression of C-MYC and the phosphorylation of CrkL in K562 cells, and real-time polymerase chain reaction （real-time PCR） was used to quantify the expression of BCR-ABL mRNA in K562 cells. The results indicated that CA induced the apoptosis of K562 cells in a time- and dose-dependent manner. CA induced apoptosis of CML MNC dose-dependently. CA inhibited the expression of BCR-ABL mRNA and C-MYC, reduced CrkL phosphorylation levels in K562 cells. It is concluded that CA induces apoptosis of CML cells in vitro. Down-regulation of the expression and function of BCR-ABL may be one of its most important anti-leukemia mechanisms.