摘要
目的观察核因子-κB(NF-κB)信号通路的阻断剂吡咯烷二硫代氨基甲酸盐(PDTC)对人白血病HL-60细胞凋亡的影响,研究其对肿瘤坏死因子α(TNF-α)、多药耐药基因1(MDR-1)表达的影响,探讨其降低HL-60细胞耐药的新机制。方法流式细胞仪检测不同浓度PDTC及PDTC(150μmol/L)联合阿糖胞苷(Ara-C)对HL-60细胞凋亡的影响;ELISA法检测不同浓度PDTC作用后HL-60细胞TNF-α水平变化;RT-PCR法分析HL-60细胞中MDR-1 mRNA的表达情况。结果不同浓度PDTC作用后HL-60细胞凋亡率均高于对照组(P<0.05),且随药物浓度的增高而增加;PDTC(150μmol/L)作用后可增强Ara-C诱导HL-60细胞凋亡;不同浓度PDTC作用后HL-60细胞TNF-α水平及MDR-1 mRNA的表达量均低于对照组(P<0.05),且随药物浓度的增高而降低。结论 PDTC可诱导HL-60细胞凋亡,增强HL-60细胞对Ara-C化疗敏感性,其机制可能与PDTC抑制NF-κB的信号转导通路,下调TNF-α、MDR-1 mRNA水平有关。
Objective To discuss the effect of pyrrolidine dithiocarbama （PDTC）, a selective inhibitor of NF-κB, on the apoptosis of human HL-60 cells and analyze the expression levels of TNF-α and MDR-1 in HL-60 treated by PDTC in order to explore the new mechanism of PDTC in drug resistance of tumor cells. Methods Human HL-60 ceils were treated with PDTC and Ara-C. The cell apoptosis was detected by flow cytometry （FCM） ; the expression levels of TNF-α were measured by Enzyme-linked immunosorbent assay （ELISA） ; the mRNA levels of MDR-1 were detected by RT-PCR. Results The apoptotic rates of HL-60 cells induced by different concentrations of PDTC were higher compared with the control （P 〈 0. 05 ）, which could enhance the cell apoptosis induced by Ara-C in a dose-dependent manner. The levels of TNF-α and MDR-1 decreased after PDTC treatment in a non-dose-dependent manner （P 〈 0. 05）. Conclusions PDTC could induce the apoptosis of HL-60 cells and enhance the chemotherapeutic sensitivity of HL-60 cells to Ara-c. PDTC may down-regulate the expression levels of TNF-α and MDR-1 by inhibiting NF-κB signal transduction.
出处
《中国小儿血液与肿瘤杂志》
CAS
2013年第2期61-64,共4页
Journal of China Pediatric Blood and Cancer
