1,25-二羟基维生素D_3抑制K562细胞增殖及其机制  

Effects of 1α,25-Dihydroxyvitamin D_3 on the proliferation and apoptosis of K562 leukemia cells and its mechanism

作　　者：张翼[1] 左文丽[2] 何玉玲[1] 周智广[1] 

机构地区：[1]中南大学湘雅二医院代谢内分泌研究所 [2]湘雅二医院血液科,湖南长沙410011

出　　处：《中国药理学通报》2006年第10期1215-1218,共4页Chinese Pharmacological Bulletin

基　　金：湖南省科技厅科技计划重点资助项目(No03SSY1009)

摘　　要：目的观察1,25二-羟基维生素D3〔1,25(OH)2D3〕对白血病细胞株K562增殖的影响并初步探讨其作用机制。方法间接免疫荧光法鉴定维生素D受体(VDR)在K562细胞的表达;四噻唑蓝法(MTT)、AO/EB、流式细胞PI单染分析细胞生长抑制率、细胞凋亡率及细胞周期;比色法检测凋亡信号蛋白———天冬酰胺特异酶切的半胱氨酸蛋白酶-3(Caspase-3)活性。结果①K562细胞核阳性表达VDR;②10-8mol.L-11,25(OH)2D3可明显抑制K562细胞增殖,促进凋亡,凋亡率从4.1%(对照组)增至26.5%,P<0.01;③1,25(OH)2D3作用后K562细胞的Caspase-3活性增加,P<0.05,提示细胞凋亡伴随着Caspaes-3活性升高。结论1,25(OH)2D3可明显抑制K562细胞增殖,促进细胞凋亡,其作用机制与Caspase-3活性增加相关。Aim To investigate effects of 1α, 25-Dihydroxyvitamin D3 on the growth inhibition, proliferation of K562 cells and to explore its mechanism. Methods The expression of vitamin D receptor （VDR） was indentified by indirect immunofluorescent stainings. Cell growth, proliferation, apoptosis and cells cycle were evaluated by MTF assay, acridine orange/ethidium bromide （AO/EB） and flow cytometry PI staining. The enzymatic activity of the caspases-3 class of K562 cells was determined by colorimetric assay. Results ① VDR was present in K562 cell nucleus; ② 10^-8 mol · L^-1 1, 25 （OH）2D3 could markedly inhibit K562 cells growth and induce cells apoptosiswith most of cells being arrested in G2/Mphase. The ratio of apoptosis increased from 4. 1% （control group） to 26.5% （ treatment group）, P 〈 0.01 ; ③ The enzymatic activity of the caspases-3 class increased significantly in cells treated with 1 α,25-Dihydroxyvitamin D3 , P 〈 0. 05, implying the development of apoptosis accompanied with the increasing caspases-3 activity. Conclusion 1α,25-Dihydroxyvitamin D3 exhibited obvious inhibitory effects on the cell proliferation, cell cycle and induced apoptosis in K562 cells. The mechanism appears to involve enhancing caspase-3 class activity.

关 键 词：1 25-二羟基维生素D3 K562细胞 细胞增殖 凋亡 CASPASE-3 

分 类 号：R322.25[医药卫生—人体解剖和组织胚胎学] R392.11[医药卫生—基础医学]