Objective We aimed to investigate the expression of IRF4 and apoptosis of the histone deacetylase inhibitor LBH589 against MM cells in vitro,and study the mechanism of apoptosis when LBH589 alone or/and combined with lenalidomide in RPMI8226 cell so as to provide a new strategy for the treatment of multiple myeloma.Methods The cell viability on the growth of RPMI8226 cell were assessed by CCK8 assay.Apoptosis were measured by flow cytometry,The Grandpad software analyzes the statistical significance and evaluates the synergistic effect of the drug.The expression level of the related transcription factor and apoptotic gene protein were determined by western blot.The cell viability on the growth of RPMI8226-R cell were assessed by CCK8.Results LBH589 combined with lenalidomide have significant effect on inhibit cell proliferation and induce apoptosis in a dose-dependent manner.Apoptosis induced by LBH589/lenalidomide alone or combination was shown to involved PARP activation,decreased Bcl-2 and Bcl-xl expression.significantly down regulated transcriptional related factors of IRF4 and c-MYC expression compared with either agent alone.Conclusion LBH589 and lenalidomide alone or combination decrease the expression of transcription factor IRF4 and c-MYC,and have a significant synergistic effect,and highly expression of IRF in RPMI8226-R reduce proliferation inhibition.%目的 体外观察组蛋白去乙酰化酶抑制剂LBH589和来那度胺作用于多发性骨髓瘤(MM)细胞后转录因子干扰素调节因子4(IRF4)表达变化以及凋亡情况及机制.方法 LBH589和来那度胺以不同浓度单独或者联合作用于RPMI8226细胞株,CCK8,Annexin V/propidium iodide染色、流式细胞仪观察细胞活力和凋亡情况,评价药物的协同效应,Western blot法检测相关转录因子及凋亡基因蛋白表达水平.结果 LBH589和来那度胺单独作用均可呈药物浓度依赖性地抑制细胞增殖、诱导细胞凋亡,两药协同效应显著.相关蛋白PARP激活,Bcl-x1、Bcl-2表达均相对下调,转录相关因子IRF4、c-MYC下调.结论 LBH589和来那度胺单独或者联合作用RPMI8226细胞株,可降低转录因子IRF4以及c-MYC的表达,两个药物合用呈显著协同效应,并且高表达IRF4的RPMI8226-R可减少其增殖抑制作用.
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