姜黄素联合STI571对K562细胞的作用及其对组蛋白去乙酰化酶8的影响  

Effect of Curcumin in Combination with STI571 on K562 Cells and Histone Deacetylase 8

作　　者：干定云[1] 陈燕[1] 何静[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：《华中科技大学学报（医学版）》2006年第4期455-458,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30271672)

摘　　要：目的研究姜黄素单用及联合STI571对K562细胞增殖与凋亡的影响,及其对组蛋白去乙酰化酶8(histonedeacetylase 8,HDAC8)的作用,探讨其克服STI571耐药的可能机制。方法四唑盐(MTT)比色法检测细胞增殖活性;Annexin-ⅤFITC/PI双染流式细胞仪检测细胞凋亡;SABC法检测细胞HDAC8的表达。结果①姜黄素和STI571分别以时间和浓度依赖的方式抑制K562细胞增殖,其36 h的IC50分别为(22.23±2.15)μmol/L和(0.21±0.03)μmol/L,而联用后对K562细胞增殖的抑制作用更为显著。STI571 0.2μmol/L与姜黄素15、30μmol/L联用36 h后的增殖抑制率分别为(72.59±2.81)%和(88.93±1.58)%。②联用姜黄素与STI571能显著增强其诱导K562细胞凋亡的能力。STI571 0.2μmol/L与姜黄素10、30μmol/L联合作用18 h后的凋亡率分别为(15.44±2.92)%和(28.16±3.22)%。③姜黄素能明显抑制K562细胞HDAC8的表达。结论姜黄素与STI571联合能明显增强其抑制K562细胞增殖、诱导凋亡的能力;抑制HDAC8的活性可能是其机制之一。Objective To investigate the influence of curcumin combined with STI517 on the proliferation and apoptosis of K562 cells and the expression of histone deacetylase 8 （HDAC8）. Methods Cell proliferation was studied by tetrazolium dye assay, the apoptosis of K562 cells was detected by flow cytometry through Annexin-V FITC/PI double stain, and the expression of HDAC8 was assayed by immunohistochemistry. Results ① Curcumin and STI571 could inhibit the proliferation of K562 cells in a time- and dose-dependent manner and their IC50 at 36 h were （22.23±2.15） μmol/L and （0.21±0.03） μmol/ L respectively, while combined use of them could reach a much higher inhibition rate; ② Combined use of eurcumin and STI571 could increase the apoptosis rates obviously. After 18 h, the apoptotic rates by combined use of 0.2 μmol/L STI571 and 10 or 30 μmol/L curcumin were （15.44±2.92） % and （28.16±_3.22）% respectively. ③ Curcumin could inhibit the expression of HDAC8 in K562 cells. Conclusion Combined use of curcumin and STI571 could increase the effect of inhibiting the prolifera tion and inducing the apoptosis of K562 cells, and the competence of HDAC8 of K562 cells might be inhibited by eureumin.

关 键 词：姜黄素 STI571 细胞株K562 组蛋白去乙酰化酶8 

分 类 号：R733.72[医药卫生—肿瘤]