组蛋白脱乙酰化酶抑制剂对Notch1受体及jagged1与jagged2配体表达的影响  

Effects of histone deacetylase inhibitor on the expression of Notch1 receptor and the ligands of jagged1 and jagged 2

作　　者：赵瑞娟[1] 乔莲[2] 杨悦[1] 赵蕾[1] 王丽红[1] 闫丽娜[1] 张志华[1] 郝长来[1] 

机构地区：[1]承德医学院附属医院血液病科,河北承德067000 [2]河北中医学院实验中心,石家庄050200

出　　处：《中国临床药理学杂志》2015年第10期861-864,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河北省自然科学基金资助项目(H2013406112)

摘　　要：目的探讨丙戊酸钠(VPA)对多发性骨髓瘤(MM)细胞株RPMI8226细胞Notch受体及配体表达的影响。方法培养RPMI8226细胞后,分为4组,对照组(空白)和小中大3个浓度(VPA 2,4,8 mmol·L-1)实验组。用不同浓度VPA处理RPMI8226细胞24,48,72 h,用四甲基偶氮唑蓝比色法检测细胞增殖抑制作用。用反转录聚合酶链式反应、蛋白免疫印迹方法检测细胞Notch1、jagged1及jagged2 mRNA和Notch1、jagged1及jagged2蛋白在VPA作用后48 h的表达。结果 VPA对RPMI8226细胞的增殖抑制作用具有明显的浓度-时间依赖效应。不同浓度VPA作用RPMI8226细胞48 h,与对照组相比,Notch1、jagged1、jagged2 mRNA和Notch1、jagged1、jagged2蛋白表达均明显降低(P<0.05),且随着VPA浓度的不断增高,各基因和蛋白的表达量逐渐降低,3个浓度VPA组间两两比较,差异均有统计学意义(P<0.05)。结论 VPA能够下调RPMI8226细胞Notch1受体、jagged1及jagged2配体的表达水平,这可能是VPA治疗多发性骨髓瘤的作用机制之一。Objective To investigate the effects of valproic acid （ VPA ） on the expression of Notch receptor and ligand in multiple myeloma （ MM ） cell line RPMI8226.Methods RPMI8226 cell line was cultured , four groups have been set up in the experiment according to the concentrations （0, 2, 4, 8 mmol· L -1 ） of VPA.When RPMI8226 cell exposed to different concentrations of VPA for 24, 48 and 72 h, the cell proliferation inhibition was measured with 3-（4,5-dimethylthiazol -2-yl）-2,5-diphemyltetra-zolium Bromide （ MTT） assay method.The change of the expression of mRNA and protein level of Notch 1 , jagged1 and jagged2 were detected by RT-PCR and Western Blot .Results The proliferation inhibition of VPA on RPMI 8226 cell in a concentration -and time-dependent manner.Compared with control group（blank）, incuba-ted with different concentrations （2, 4, 8 mmol· L-1 ） of VPA for 48 h, the expression of Notch1,jagged1,jagged2 mRNA and protein were gra-dually decreased , with statistical significance （ P〈0.05 ） , with the in-crease of VPA concentration.Among the different VPA groups ,mutiple comparisons , the differences were statistically significant （ P 〈0.05 ） . Conclusions VPA could down -regulate the expression of Notch 1 ,jagged1 and jagged2 in RPMI8226 cell, which may be one of the mechanism of action of VPA on the treatment of multi-ple myeloma.

关 键 词：多发性骨髓瘤 丙戊酸钠 NOTCH1 JAGGED1 jagged2 RPMI8226细胞 

分 类 号：R971.6[医药卫生—药品] R968[医药卫生—药学]