硼替佐米对伊马替尼耐药细胞系K562／G01药物敏感性的影响  

Effect of bortezomib on the drug sensitivity of imatinib resistant K562/G01 cells

作　　者：周英[1] 马梁明[1] 李晓宇[2] 张华屏[3] 王涛[1] 牛燕燕[1] 任瑞瑞[1] 

机构地区：[1]山西医科大学第二医院血液科,030001 [2]山西医科大学生理教研室 [3]山西医科大学中心实验室

出　　处：《中华血液学杂志》2011年第6期392-395,共4页Chinese Journal of Hematology

摘　　要：目的探讨蛋白酶体抑制剂硼替佐米对伊马替尼耐药细胞系（K562／G01）药物敏感性的影响及作用机制。方法采用MTT法观察伊马替尼单用与联用硼替佐米对K562／G01细胞增殖的影响。流式细胞技术检测细胞周期的变化。实时荧光定量PCR检测COX-2、多药耐药（mdrl）基因的表达。结果联合10、20nmoL／L硼替佐米能明显增强K562／G01细胞的伊马替尼药物敏感性，逆转倍数分别为1．83、2．72倍，进一步计算表明两药联合具有协同作用。流式细胞技术检测显示硼替佐米作用后细胞周期向G2／M期转化。实时荧光定量PCR检测显示K562／G01细胞高表达的COX-2和mdrl基因，硼替佐米作用后均表达下调。结论硼替佐米能增强K562／G01细胞对伊马替尼的敏感性，其机制可能与细胞周期的G2／M期阻滞，抑制COX-2和mdrl的表达有关。Objective To explore the effect of bortezomib （BOR） on the drug sensitivity of imatinibresistant chronic myeloid leukemia cell line K562/G01 cell and its mechanism. Methods MTT assay was used to detect the inhibition effect of cell growth, flow cytometry to cell cycle, and real time-PCR to the ex- pression of COX-2 and mdrl mRNA. Results Combination of l0 and 20 nmol/L BOR with imatinib could significantly enhance the sensitivity of K562/GOI to imatinib, the reverse factor was 1.83 and 2.72-fold respectively. Cell cycle arrested at G2/M phase could be observed by flow cytometry on BOR treatment. The over-expression of COX-2 and mdrl could be down-regulated by BOR. Conclusions BOR can enhance the imatinib sensitivity of imatinib resistant K562/G01 cell. The mechanism may be related to cell cycle phase arrested at G2/M and down-regulation of COX-2 and mdrl expression.

关 键 词：硼替佐米 K562/G01细胞 抗药性 环氧化酶-2 基因 mdrl 

分 类 号：R965[医药卫生—药理学]