摘要
目的:观察组蛋白去乙酰化抑制剂suberic bishydroxamate(SBHA)对人急性髓系白血病(AML)细胞株的杀伤作用。方法:将不同浓度的SBHA分别作用于对数生长期的AML细胞24 h,MTT比色法检测药物对细胞的生长抑制作用;应用流式细胞术(FACS)检测细胞凋亡率,Western blot法检测药物处理后Caspase途径和凋亡相关蛋白的改变。结果:SBHA能显著抑制AML细胞株U937、KG-1及Kasumi-1细胞的生长。AnnexinV-PI双标记法及FACS分析结果证实,SBHA能显著诱导白血病细胞的凋亡,激活Caspase-3、Caspase-9、Caspase-8,下调抗凋亡蛋白Bcl-2及Bcl-xl的表达,下调Survivin、XIAP及cIAP的表达。结论:组蛋白去乙酰化抑制剂SBHA能显著抑制人AML细胞株的增殖、促进其凋亡,对凋亡相关蛋白的调控是其作用机制之一。
Objective： To investigate the effect of histone deacetylase inhibitor suberic bishydroxamate（SBHA） on human acute myeloid leukemia（AML） cell lines.Methods： AML U937,KG-1 and Kasumi-1 cells were treated with SBHA.Cell growth was measured by MTT assay.Apoptosis was determined using flow cytometry.Activation of Caspase pathway and expression of apoptosis regulator proteins were detected by Western blot.Results： SBHA significantly induced growth arrest and apoptosis in U937,KG-1 and Kasumi-1 cells.Enhanced apoptosis was observed in SHBA group evidenced by strong activation of Caspase-9,Caspase-8 and Caspase-3.SHBA treatment resulted in down-regulation of anti-apoptotic protein Bcl-2 and Bcl-xl expression;down-regulated expression of antiapoptotic proteins survivin,XIAP and cIAP was also detected after SBHA treatment.Conclusion： SBHA can effectively kill AML cells by inhibiting cell growth and inducing apoptosis,which is associated with the activation of Caspase pathway and regulation of apoptotic related proteins.
出处
《浙江大学学报（医学版）》
CAS
CSCD
北大核心
2012年第5期491-497,共7页
Journal of Zhejiang University(Medical Sciences)
基金
浙江省自然科学基金杰出青年团队(No.R2090392)
浙江省科技厅公益性技术应用研究计划(No.2012C37103)资助项目
浙江省理工大学科研启动基金(No.1016834-Y)
