木香烃内酯通过JAK/STAT通路抑制K562细胞增殖研究

目的:探讨木香烃内酯对慢性髓系白血病细胞系K562细胞的增殖抑制作用及机制。方法:采用CCK-8法检测木香烃内酯对K562细胞的增殖抑制作用,流式细胞术检测细胞凋亡率及活性氧(reactive oxygen species,ROS)水平,Western blot检测相关蛋白的表达。结果:木香烃内酯能够明显抑制K562细胞增殖,其24 h半数有效抑制浓度(IC50)约为(15.70±2.13)μmol/L(P<0.05);15μmol/L木香烃内酯分别作用K562细胞0、24和48 h均能够诱导K562细胞凋亡,凋亡率由(1.77±0.59)%分别增加到(17.68±2.84)%、(30.65±4.54)%(P<0.05);木香烃内酯能够明显增加细胞内ROS的水平,由(3.52±1.08)%分别增加到(23.56±3.52)%,(36.68±4.22)%(P<0.05);木香烃内酯能够显著降低BCL-2、p-JAK2、p-STAT3的表达,上调BAX、细胞色素C、cleaved-caspase-3、cleaved-PARP的表达水平。结论:木香烃内酯能够通过JAK/STAT信号通路诱导K562细胞凋亡,从而抑制其细胞增殖。

Costunolide Suppresses Proliferation of K562 Cells through JAK/STAT Signaling Pathway

Objective:To investigate the inhibitory effect of costunolide on the proliferation of human chronic myeloid leukemia cell line K562 cells and the underlying mechanisms.Methods:The effect of costunolide on the viability of K562 cells was detected by CCK-8 assay.The cell apoptosis and the level of ROS in K562 cells were detected by flow cytometry.The expression level of related proteins were analyzed using Western blot.Results:The CCK-8 viability assay showed that costunolide at the gradient concentrations of 0-50μmol/L significantly inhibited the proliferation of K562 cells after exposure for 24 h.The IC50 value of costunolide was approximately 15.70±2.13μmol/L,with statistically significant difference(P<0.05).Treatment with 15μmol/L costunolide for 24 and 48 h induced apoptosis of K562 cells with the apoptotic rate significantly increasing from(1.77±0.59)%in the control group to(17.68±2.84)%and(30.65±4.54)%(P<0.05)respectively.Furthermore,following treatment,the level of ROS was significantly increased,from(3.52±1.08)%to(23.56±3.52)%and(36.68±4.22)%(P<0.05).The study results also revealed that costunolide treatment significantly inhibited the expression of p-JAK2,p-STAT3 and BCL-2,and increased the expression of BAX,cytochrome C,cleaved-caspase-3 and cleaved-PARP.Conclusion:Costunolide suppresses the proliferation of K562 cells through JAK/STAT signaling pathway.