【摘要】 目的研究核转录因子κB与急性早幼粒细胞性白血病(APL)细胞对三氧化二砷(As2O3)敏感性降低的关系。方法应用四甲基偶氮唑蓝(MTT)法进行半数抑制浓度(IC50)测定以评估细胞对药物的敏感度;免疫细胞化学检测NF-κBp65的核转位;免疫组织化学染色法鉴定核转录因子κB抑制剂MG-132对耐药细胞P-gp表达的影响。结果对照组比药物处理组的IC50高6.4倍;药物处理组P-gp的表达阳性率为10.17%,对照组的P-gp的表达阳性率为30.43%,两者相比较差异显著(P<0.05)。结论用As2O3治疗APL的同时可能会促进NF-κBp65的核转位和NF-κB的活化。抑制NF-κB的激活有助于增强As2O3对急性早幼粒细胞性白血病细胞的杀伤效应;NF-κB抑制剂MG-132可以明显抑制As2O3引起的P-gp的表达以及NF-κB的活化,从而显著提高急性早幼粒细胞性白血病细胞对As2O3的敏感性。更多还原

【Abstract】 Objective To investigate the relationship between drug resistance mechanism and nuclear factor kappa B(NF-κB) in acute promyelocytic leukemia(APL). Methods The IC50 value of arsenic trioxide was evaluated by MTT assay. The protein expression of P-glycoprotein(P-gp) was measured by Western blot. The expression of NF-κB p65 were detected in APL cells. Results The IC50 value of arsenic trioxide was (33. 34 ± 1. 28 )μmol/L in APL cells,which decreased to (5. 2 ± 0. 88) μmol/L(P < 0. 05) after combination with MG-132. When NF-κB activation was inhibited by MG-132,the protein expression of P-gp had marked changed. The NF-κB p65 protein was expressed only in cytoplasm of APL cells,and expressed in both cytoplasm and cytoblast of APL cells after using arsenic trioxide. Conclusion NF-κB is an important central link of drug resistance mechanism of APL cells. The inhibition of NF-κB activiation may partly reverse the resistance of APL cells against arsenic trioxide.更多还原