姜黄素对人淋巴瘤Raji细胞组蛋白H3乙酰化作用的影响  

Effect of Curcumin on Acetylation of Histone H3 in Human Lymphoma Cell Line Raji

作　　者：李新刚[1] 陈燕[1] 吴青[1] 孙春艳[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,湖北武汉430022

出　　处：《癌症》2006年第5期582-586,共5页Chinese Journal of Cancer

基　　金：国家自然科学基金项目(No.30271672)~~

摘　　要：背景与目的:表观遗传改变是肿瘤发生的一个重要原因,具有表观遗传修饰作用的甲基化转移酶抑制剂和去乙酰化酶抑制剂可以抑制肿瘤增殖诱导凋亡。本研究探讨姜黄素对Raji细胞组蛋白H3的乙酰化作用和细胞周期素依赖性激酶抑制剂p21WAF1/CIP1基因表达的影响。方法:用25μmol/L姜黄素作用Raji细胞不同时间,Westernblot分析乙酰化组蛋白H3和p21WAF1/CIP1变化;RT-PCR检测p21WAF1/CIP1基因表达;染色质免疫沉淀分析p21WAF1/CIP1的启动子基因位点组蛋白H3乙酰化水平;流式细胞术检测细胞周期变化。结果:姜黄素提高p21WAF1/CIP1的启动子基因位点组蛋白H3乙酰化水平1.9倍;使p21WAF1/CIP1mRNA合成增加和蛋白表达上调,在24h时分别增加了4.2倍和5.1倍;24h阻滞细胞在G2/M期,36h阻滞在G0/G1期。结论:姜黄素通过表观遗传修饰作用,调节p21WAF1/CIP1启动子基因位点组蛋白H3乙酰化水平,促进p21WAF1/CIP1基因转录,阻滞Raji细胞周期进程。BACKGROUND ＆ OBJECTIVE： Epigenetic change is an important mechanism of oncogenesis. The inhibitors of methyltransferases and deacetylases, with epigenetic modificative effects, could inhibit proliferation and induce apoptosis of tumor cells. This study was to investigate the effects of curcumin on the acetylation of histone H3 and the expression of p21^wAF1/CIP1 gene in human lymphoma cell line Raji. METHODS. Raji cells were treated with 25 μmol/L curcumin. The levels of acetylated histone H3 and p21^WAF1/CIP1 were detected by Western blot, the expression of p21w~ gene was detected by reverse transcription-polymerase chain reaction （RT-PCR）, and the level of acetylated histone H3 at the site of p21^WAF1/CIP1 promoter gene was examined by chromatin immunoprecipitation assay. Cell cycle distribution was studied by flow cytometry. RESULTS.. Curcumin induced hyperacetylation of histone H3 at the site of p21^WAF1/CIP1 promoter by 1.9 folds, and enhanced the levels of p21^WAF1/CIP1 mRNA by 4.2 folds and protein by 5.1 folds 24 h after treatment. Raji cells were arrested at G2/M phase when treated with curcumin for 24 h, and at G0/G1 phase when treated for 36 h. CONCLUSION. Curcumin, with epigenetic modificative effects, could enhance the acetylayion of histone H3 at the site of p21^WAF1/CIP1 promoter gene, improve transcription of p21^WAF1/CIP1 gene, and arrest cell cycle progression of Raji cells.

关 键 词：姜黄素 表观遗传修饰 P21^WAF1/CIP1 细胞周期 淋巴瘤 RAJI细胞 组蛋白H3 

分 类 号：R733.1[医药卫生—肿瘤]