摘要
目的探讨去铁胺对柔红霉素(DNR)诱导多药耐药基因MDR1及核因子κB(NFκB)表达的影响,初步了解NFκB与MDR1表达、细胞内铁代谢的关系。方法以DNR单用或联合应用25μmol/L去铁胺(DFO)为处理因素作用于人红白血病细胞株K562,应用RTPCR法、流式细胞分析技术分别检测对照组、DNR组和DNR+DFO组K562细胞MDR1mRNA和P糖蛋白(Pgp)的表达情况,同时采用免疫组织化学染色法检测NFκB的表达及活性情况。结果与对照组相比,DNR可同时诱导MDR1mRNA、Pgp表达和NFκB活化(P<0.05);25μmol/LDFO联合DNR可显著抑制DNR诱导的MDR1mRNA、Pgp的表达及NFκB的活化(P<0.05)。结论去铁胺可减少柔红霉素诱导的MDR1、Pgp表达,其机制可能与铁剥夺后降低了柔红霉素诱导的K562细胞的氧化应激反应,进而影响NFκB的活化有关。
Objectives To investigate the effect of desferioxamine （DFO） on the expression multidrug resistance gene 1 （MDR1）, the activation of nuclear factor KB （NFKB） in I（562 cells induced by daunorubicin （DNR）, and to study their relationships with intracellular iron metabolism. Methods Reverse transcription-PCR and flow cytometry were used to detect the mRNA expression level of MDR1 and P- glycoprotein （Pgp） in K562 ceils treated with DNR only or DNR associated with 25 μmol/L iron chelator DFO. The expression and activation of NFκB were determined by immunocytochemistry. Untreated K562 cells were used as control. Results Compared to the control group, the expression of MDR1 and the activation of NFκB were induced by DNR （P 〈 0.05） . The addition of 25 μmol/L DFO significantly inhibited the expression of MDR1 and Pgp and the activation of NFκB induced by DNR （P 〈 0.05） . Conclusions Desferioxamine could decrease the expression of MDR1 and Pgp in K562 cells induced by DNR. Iron deprivation might have suppressed the reactions to oxidative stress and subsequently affected the activation of NFκB.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2007年第1期47-50,57,共5页
Journal of Clinical Pediatrics
关键词
白血病
多药耐药基因
去铁胺
核因子ΚB
leukemia
muhidrug resistance gene 1
desferioxamine
nuclear factor κB
