不同浓度硼替佐米对柔红霉素诱导的K562耐药细胞株ERK、JNK及P38表达的影响  

Effect of Different Concentrations of Bortezomib on the Expression of ERK、JNK and P38 in Daunorubicin-resistant K562 Cells

作　　者：付倍蓓[1] 范莹[2] 郝良纯[1] 廖爱军[1] 刘卓刚[1] 

机构地区：[1]中国医科大学盛京医院血液病治疗中心,辽宁沈阳110022 [2]中国医科大学盛京医院第一微创外科,辽宁沈阳110004

出　　处：《中国实验血液学杂志》2011年第3期671-675,共5页Journal of Experimental Hematology

摘　　要：本研究旨在观察蛋白酶体抑制剂硼替佐米(bortezomib,PS-341)对柔红霉素(daunorubicin,DNR)诱导的K562白血病耐药细胞株ERK、JNK及P38表达的影响,探讨硼替佐米逆转耐药的分子机制。用四甲基偶氮唑盐微量酶反应比色法(MTT法)进行耐药细胞株和硼替佐米细胞毒性的判定。以100nmol/L DNR单用或联合应用1及10nmol/L PS-341作用于K562耐药细胞株36小时,检测各组ERK、JNK及P38的表达情况,检测各组细胞凋亡率。结果表明:与DNR组相比,PS-341联合DNR可抑制ERK和P38的表达,增加JNK的表达(p<0.05)。结论 :PS-341可显著抑制K562耐药细胞株ERK和P38的表达,增加JNK的表达;PS-341通过MAPK途径逆转细胞耐药,促进细胞凋亡。The aim of this study was to investigate the effect of proteasome inhibitor bortezomib on the expression of ERK, JNK, and P38 in daunorubicin （DNR）-resistant K562 cells and its mechanism. MTT method was used to determine the durg-resistant K562 cells and the cellular toxicity of bortezomib; Western blot was used to detect the expression of protein ERK, JNK and P38 in K562 cells after treatment with 100 nmol/L DNR alone or combined with 1 nmol/L and 10 nmol/L bortezomib for 36 hours. Flow cytometry assay was used to detect the apoptosis rate in each group cells. The results indicated that the expression of ERK and P38 were significantly suppressed（p 〈 0.05 ） and the expression of JNK was significantly enhanced （p 〈 0.05 ） in the cells treated by DNR combined with bortezomib. It is concluded that bortezomib can decrease the expressions of protein ERK and P38 and enhance the expression of JNK, the bortezomib reverses the cellular drug-resistance and promote cell apoptosis through MAPK pathway.

关 键 词：硼替佐米 柔红霉素 K562细胞 ERK JNK P38 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]