硼替佐米联合5-氮杂胞苷对K562细胞凋亡和SHIP基因表达的影响  

Effects of Bortezomib Combined with 5-azacytidine on the Apoptosis of K562 Cells and Expression of SHIP mRNA

作　　者：贾志强[1] 魏玉涛[1] 魏玉莲[2] 苏薇[1] 于春霞[1] 陶金[3] 戎红旗[1] 

机构地区：[1]保定市第一医院血液科,河北保定071000 [2]河北省第六人民医院临床六科,河北保定071000 [3]保定市儿童医院外科,河北保定071000

出　　处：《中国实验血液学杂志》2014年第5期1291-1294,共4页Journal of Experimental Hematology

摘　　要：本研究旨在探讨硼替佐米联合5-氮杂胞苷对K562细胞凋亡和SHIP mRNA表达的影响。用不同浓度硼替佐米和5-氮杂胞苷处理K562细胞24 h,采用MTT比色法检测细胞增殖活性,流式细胞术检测细胞凋亡,RTPCR法检测SHIP基因mRNA的表达。结果表明:5-20 nmol/L硼替佐米对K562细胞增殖均有一定抑制作用,并随着浓度增加抑制作用逐渐增强。硼替佐米和5-氮杂胞苷联合处理组对细胞的抑制作用比同剂量两药单用时都显著增强(P<0.05)。硼替佐米能促使K562细胞凋亡,且随浓度增加而凋亡增多,联合处理组对细胞的凋亡作用比同剂量单药作用时显著增强(P<0.01)。硼替佐米能下调K562细胞SHIP mRNA的表达,且随着药物浓度增加,表达逐渐降低,联合处理组与同剂量单药组相比更显著下调SHIP mRNA表达(P<0.05)。结论:硼替佐米或5-氮杂胞可以下调K562细胞中SHIP mRNA的表达,并可能通过此机制诱导K562细胞凋亡,两药具有协同作用。This study was aimed to investigate the effects of bortezomib combined with 5-azacytidine on the apoptosis of K562 cells and expressiom of SHIP mRNA.The K562 cells were cultured and treated with different concentrations of bortezomib,5-azacytidine or their combination for 24 hours.Then,the expression of SHIP mRNA was detected by RTPCR,the cell proliferation was analyzed by using MTr assay and flow cytometry.The results showed that 5-20 nmol/L bortezomib could effectively inhibit the proliferation of K562 and this inhibitory effect gradually enhanced along with the increase of bortezomib concentration,the group of bortezomib combined with 5-azacytidine showed more inhibitory effect on K562 cells than that of bortezomib or 5-azacytidine alone.The bortezomib could promote the apoptosis of K562 cells in a dose-dependent manner,and this apoptotic effect was higher in group of bortezomib combined with 5-azacytidine than that in group of bortezomib or 5-azacytidine alone.Bortezomib could down-regulated the expression of SHIP mRNA in a dose-dependent manner,and this down-requlated effect was higher in group of bortezomib combined with 5-azacytidine than that in group of bortezomib or 5-azacytidine alone.It is concluded that bortezomib and 5-azacytidine can induce apoptosis by inhibiting the expression of SHIP mRNA in K562 cells.The combination of bortezomib with 5-azacytidine displays a synergetic effect.

关 键 词：硼替佐米 5-氮杂胞苷 SHIP MRNA K562细胞 

分 类 号：R733.7[医药卫生—肿瘤]