不同浓度硼替佐米对K562/DNR细胞株NF-κB,IκB及P-gp表达的影响
Effects of different concentrations of bortezomib on the expression of NF-κB, IκB and P-gp of DNR-resistant K562 cells
廖爱军 1杨威 1付倍蓓 1李迎春 1张嵘 1刘卓刚1
作者信息
- 1. 中国医科大学附属盛京医院血液科,辽宁,沈阳,110004
- 折叠
摘要
目的:观察不同浓度硼替佐米(商品名万珂,PS-341)对柔红霉素(DNR)诱导的K562耐药细胞株(K562/DNR)核因子-κB(NF-κB)、抑制蛋白κB(IκB)及P-糖蛋白(P-gp)表达的影响,探讨PS-341逆转耐药的分子机制.方法:四甲基偶氮唑盐微茸酶反应比色法(MIT法)进行耐药细胞株和PS-341细胞毒性的判定.以100 mg/L DNR单用或联合应用0.4,4,40μg/L PS-341作用于K562/DNR 36 h,检测各组NF-κb,IKB及P-gP表达情况,并测定NF-κB活性,检测各组细胞凋亡率.结果:与阴性对照组相比,DNR可诱导NF-κB表达上调、IκB表达下调、P-gp表达上调;加用PS-341可显著抑制NF-κB表达,同时使IκB表达增加、P-gP表达下降,上述作用随PS-341浓度增加而增强.NF-κB活性(%)检测示:DNR组为25.9±2.5,DNR+0.4μg/L PS-341组为20.3±2.0,DNR+4μg/L PS-341组为6.1±2.5,DNR+40μg/LPS-341组为4.6±1.6,加入PS-341后,NF-κB活性受抑,该作用随PS-341浓度增加而增强.细胞凋亡率(%)检测结果示:DNR组为22.5±4.6,DNR+0.4μg/L PS-341组为31.0±5.2,DNR+4μg/L PS-341组为43.6 ±7.7,DNR+40μg/LPS-341组为56.0±9.3,加入PS-341后可提高DNR引起的细胞凋亡率,该作用随PS-341浓度的增加而增强.结论:PS-341可逆转白血病细胞耐药,该作用呈浓度依赖性.
Abstract
AIM: To observe the effects of bortezomib (PS-341) on the expression of NF-κB, IκB and P-gp of K562 cells inducedby daunorubicin (K562/DNR). METHODS: MTr method was used to determine the drug-resistant K562 cells and the cellular toxicity of bortezomib; Detect the expression of NF-κB, IκB and P-gp of K562/DNR 36 h after receiving the treatment of 100 mg/L DNR only or added with 0.4,4 and 40 gμ/L bortezomib. Detect the apoptosis rate in each group respectively and the activity of NF-κB was detected by ELISA method. RESULTS: Compared with the control group, the expressions of NF-κB and P-gp in K562/DNR group could be induced by DNR. When K562/DNR cells were cultured with bortezomib,the expressions of NF-κB and P-gp induced by DNR were significantly suppressed and IκB was increased, these effects increased with the increase of the concentration of PS-341. The results of NF-κB's activity showed that the team of DNR was 25.9±2.5, DNR + 0.4 μg/L PS-341 was 20.3 ±2.0,DNR +4 μL PS-341was 6.1+2.5,DNR +40 μg/L PS-341 was 4.6±1.6. The activity of NF-κB was suppressed when PS-341 was added in. The results of apaptosis rate (%) showed that the team of DNR was 22.5±4.6, DNR + 0.4 μg/L PS-341 was 31.0 ± 5.2,DNR +4 μg/L PS-341was 43.6±7.7, DNR +40 μg/L PS-341 was 56.0 ± 9.3. The apoptosis rate in-creased when K562/DNR cells were cultured with bortezomib, these effects increased with the increase of concentration of bortezomih. CONCLUSION: Bortezomib ceuld convert the cellulardrug resistance and this effect showed the characteristic of concentration-dependent pattern.
关键词
蛋白酶体抑制剂/NF-κB/I-κB/P-糖蛋白/K562细胞Key words
proteasome inhibitor/NF-kappa B/I-kappa B/P-glycoprotein/K562 cells引用本文复制引用
基金项目
辽宁省教育厅高等学校科研项目计划(20060985)
出版年
2009
NETL
NSTL
万方数据