姜黄素调节B淋巴瘤细胞p300和HDAC1的研究  

Regulatory Effect of Curcumin on p300 and HDAC1 in B-NHL Cells

作　　者：吴青[1] 陈燕[1] 李新刚[1] 唐元艳[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院血液病研究所,武汉430022

出　　处：《中国实验血液学杂志》2006年第2期293-297,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金资助项目;编号:30271672

摘　　要：p300是一种具有组蛋白乙酰化酶活性的转录辅助因子,HDAC1是一种组蛋白去乙酰化酶。本研究查明姜黄素对B-NHL细胞株Raji细胞增殖的影响,并探讨这种影响与p300以及HDAC1转录调节表达的关系。以不同浓度(6.25-50μmol/L)的姜黄素作用于体外培养的Raji细胞,用MTT法检测细胞生长抑制率,Annexin-V-FITC/PI双标流式细胞术检测细胞的凋亡率和应用RT-PCR和Westernblot法检测Raji细胞中HDAC1和p300的mRNA表达和蛋白含量的变化。结果表明:姜黄素对Raji细胞抑制作用呈明显的时效和量效关系。24小时的IC50为25μmo/L;姜黄素能够诱导Raji细胞凋亡,凋亡率为14.38%-61.18%,并呈浓度依赖性。姜黄素明显抑制HDAC1和p300的活性和表达。在IC50浓度时,随着时间的延长,其p300和HDAC1mRNA表达和蛋白含量逐渐降低,呈时间依赖性,与对照组相比有显著性(P<0.05)。结论:姜黄素对B细胞淋巴瘤细胞系Raji细胞具有抗肿瘤细胞的增殖作用,并促进其凋亡。姜黄素能够抑制转录共激活因子p300及组蛋白去乙酰化酶HDAC1活性和表达,可能是其作用机制之一。The purpose of this study was to investigate the effect of curcumin on proliferation of B-NHL Raji cell line and explore the relationship between this effect and regulatory expression of p300 and HDAC1 transcription. The in vitro cultured Raji cells were treated with curcumin at various concentrations （6.25 -50 μmol/L） and at different time points （0, 6, 12, 24 and48 hours）, the inhibitory ratio of cell growth was measured by MTT assay, the cell apoptosis rate was detected by flow cytometry with Annexin V-FITC/PI double staining, the changes of p300 and HDAC1 mRNA expression and protein level in Raji cells were determined by RT-PCR and Western blot. The results showed that the curcumin could inhibit Raji cell proliferation in significant time-and concentration-dependent manners, IC50 at 24 hours was 25 μmol/L; the curcumin could induce apoptosis of Raji cells in concentration-dependent manner, apoptosis rate was 14.38% -61.18%. The curcumin significantly inhibited activity and expression of p300 and HDAC1. At IC50 concentration, expression of p300 and HDACI mRNA and protein level decreased with time-dependent manner, difference between tested and control groups was significant （ P 〈 0.05 ）. It is concluded that the curcumin can inhibit proliferation of B-NHL Raji cells and promote apoptosis of those cells. Curcumin can inhibit the activity and expression of the transcriptional co-activator p300 and HDAC1, which may be involved in its pharmacological mechanisms on B lymphoma cells.

关 键 词：姜黄素 B淋巴瘤 RAJI细胞 P300 HDAC1 

分 类 号：R733.1[医药卫生—肿瘤] R979.1[医药卫生—临床医学]