木香烃内酯通过PI3K/AKT通路诱导K562/ADR细胞凋亡

Costunolide Induces Apoptosis of K562/ADR Cells through PI3K/AKT Pathway

目的:探讨木香烃内酯对慢性粒细胞性白血病细胞耐药细胞株K562/ADR细胞增殖及凋亡的影响及其机制。方法:运用CCK-8法检测细胞增殖,流式细胞术检测细胞凋亡,Western blot检测相关蛋白的表达。结果:选用木香烃内酯0.01、0.1、0.25、0.5、1、2.5、5、10、25、50和100μmol/L作用K562/ADR细胞72h后,结果显示,木香烃内酯能够显著抑制K562/ADR细胞增殖,且呈浓度依赖性(r=0.9886),半数有效抑制浓度约为10.86±0.99μmol/L,差异有统计学意义(P<0.05)。选用木香烃内酯10及15μmol/L能显著诱导K562/ADR细胞凋亡,细胞凋亡率分别为14.80%±3.27%和33.2%±5.03%,与对照组(4.30%±0.62%)相比差异具有统计学意义(P<0.05)。Western blot结果显示,木香烃内酯能够明显下调p-AKT、p-PI3K、BCL-2的表达,上调激活型caspase-3、cleaved-PARP的表达。结论:木香烃内酯抑制K562/ADR细胞增殖并诱导细胞凋亡可能是通过调控PI3K/AKT通路实现的。

Objective:To explore the effects of costunolide on the proliferation and apoptosis of human chronic myeloid leukemia drug resisitant cell line K562/ADR and its mechanism.Methods:The proliferation of the cells was assessed by CCK-8 assay,while flow cytometry was used to detect the apoptosis of the cells.The related-proteins were detected by using Western blot.Results:The proliferation of K526/ADR cells was significantly inhibited by costunolide in a dose-dependent manner(r=0.9886)after treated by 0.01,0.1,0.25,0.5,1,2.5,5,10,25,50 and 100μmol/L costunolide for 72 h,and IC50 value of costunolide on K562/ADR cells was about(10.86±0.99)μmol/L(P<0.05).The apoptosis of K562/ADR cells could be induced by costunolide(10 and 15μmol/L)significantly,the rate of apoptosis was 14.80%±3.27%,33.2%±5.03%,respectively,which in comparison with a significantly difference as compared with the control group(4.30%±0.62%)(P<0.05).Western blot showed that costunolide could down-regulated the expression of p-AKT,p-PI3K,BCL-2,and up-regulated the expression of cleaved-caspase-3,cleaved-PARP significantly.Conclusion:Costunolide could inhibit the proliferation and apoptosis of K562/ADR cells through regulation of PI3K/AKT pathway.