摘要
目的:探讨抗寄生虫药芬苯达唑对慢性髓系白血病细胞K562的作用及机制。方法:采用CCK-8法检测芬苯达唑对K562和正常人外周血单个核细胞(PBMC)生长的影响;台盼蓝拒染实验检测芬苯达唑对K562细胞活力的影响;瑞氏染色观察芬苯达唑对K562细胞形态的影响;流式细胞术检测芬苯达唑对K562细胞周期分布的影响;Western blot检测芬苯达唑对K562细胞周期相关蛋白表达的影响;免疫荧光观察芬苯达唑对K562细胞核的改变。结果:芬苯达唑能够显著抑制K562细胞的生长,而对PBMC生长无明显影响;进一步的研究发现,芬苯达唑显著抑制K562细胞增殖并诱导细胞发生G_2/M期阻滞;芬苯达唑处理K562细胞后,细胞分裂周期蛋白25C(Cdc25C)磷酸化、周期素依赖性激酶1(Cdk1)-Tyr15去磷酸化以及cyclin B1磷酸化增加;免疫荧光结果证实芬苯达唑诱导K562多核细胞增多(P<0.01),发生有丝分裂灾难。结论:芬苯达唑通过调控周期相关蛋白诱导K562细胞发生G_2/M期阻滞。
AIM： To investigate the effect of fenbendazole （FBZ） on the proliferation of human chronic my-elogenous leukemia （ CML） cell line K562. METHODS ： The CCK-8 assay was used to detect the effect of FBZ on viabili-ty of the K562 cells and normal peripheral blood mononuclear cells （PBMC）. The cell growth was measured by the method of Trypan blue exclusion. The cell cycle was analyzed by flow cytometry. The cell cycle-related proteins were detected by Western blot. RESULTS ： The growth of K562 was significantly inhibited by FBZ. However, it elicited little cytotoxic effect on PBMC. Furthermore, FBZ induced G2/M phase arrest and mitotic catastrophe in the K562 cells based on the changes of nuclear morphology, DNA content, mitotic marker analysis and the number of polykaryocytes. CONCLU-SION ：Fenbendazole significantly inhibits the proliferation of K562 cells and induces cell cycle arrest at G2/M phase by the regulation of cell cycle-related proteins.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2017年第6期1012-1016,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81400125
No.81372826)
教育部博士点新教师类资助项目(No.20133321120003)
浙江省自然科学基金资助项目(No.LQ13H080002)
关键词
芬苯达唑
慢性髓系白血病
增殖抑制
G2/M期阻滞
Fenbendazole
Chronic myelogenous leukemia
Proliferation inhibition
G2/M phase arrest
