Yang Chunhui, Cai Hong, Yan Jiangzhou, Yang Jingbo, Sun Meiyan, Meng Xiuxiang, Ma Tonghui
Department of Laboratory Hematology, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
Zhonghua Xue Ye Xue Za Zhi. 2014 Jun;35(6):515-8. doi: 10.3760/cma.j.issn.0253-2727.2014.06.009.
To explore the inhibitory effect of alantolactone on the proliferation of adriamycin-resistant human chronic myelogenous leukemia cell line K562/ADR cells and its mechanism.
K562/ADR cells were treated with various concentrations of alantolactone (0, 1, 2, 4, 6, 8, and 10 μmol/L) for different time points. Cell viability was analyzed with MTT assay. The effect of alantolactone on the apoptosis of K562/ADR cells was measured by flow cytometry. The expression of apoptosis-related proteins after treatment with alantolactone was analyzed using Western blot.
Alantolactone could effectively inhibit the proliferation of K562/ADR cells in dose- and time- dependent manner, the IC50 value of alantolactone treatment of K562/ADR cells for 24 h was 4.7 μmol/L (P<0.05). Flow cytometric analysis displayed that the apoptotic rates were 1.35%, 16.91%, 29.61% and 46.26%, respectively, after treatment with alantolactone at 0, 2.5, 5 and 7.5 μmol/L. Meanwhile, the expression of Bcl-2 and BCR-ABL proteins were significantly decreased and that of Bax, cytochrome C, cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP increased by alantolactone treatment.
Alantolactone had obvious inhibitory effect on the proliferation of K562/ADR cells through the caspase dependent mitochondrial(or intrinsic)apoptotic pathway.
探讨土木香内酯对阿霉素耐药的人慢性髓性白血病细胞系K562/ADR细胞增殖的抑制作用及其机制。
用不同浓度(0、1、2、4、6、8和10 μmol/L)的土木香内酯处理K562/ADR细胞不同时间点。采用MTT法分析细胞活力。通过流式细胞术检测土木香内酯对K562/ADR细胞凋亡的影响。用蛋白质免疫印迹法分析土木香内酯处理后凋亡相关蛋白的表达。
土木香内酯能以剂量和时间依赖性方式有效抑制K562/ADR细胞的增殖,土木香内酯处理K562/ADR细胞24 h的IC50值为4.7 μmol/L(P<0.05)。流式细胞术分析显示,用0、2.5、5和7.5 μmol/L土木香内酯处理后,凋亡率分别为1.35%、16.91%、29.61%和46.26%。同时,土木香内酯处理使Bcl-2和BCR-ABL蛋白表达显著降低,而Bax、细胞色素C、裂解的半胱天冬酶-9、裂解的半胱天冬酶-3和裂解的PARP表达增加。
土木香内酯通过半胱天冬酶依赖性线粒体(或内源性)凋亡途径对K562/ADR细胞的增殖有明显抑制作用。