柚皮素对K562/A02细胞MDR1 mRNA/P-gp的影响及机制研究  

Influence of naringenin on MDR1 mRNA/P-gp in K562/A02 cells

作　　者：朱宏平[1] 靳高凤 陈亚军[1] 李新华[2] 张红[1] 黄世博[1] 夏春华[1] 熊玉卿[1] 

机构地区：[1]南昌大学临床药理研究所 [2]南昌大学医院

出　　处：《中国临床药理学与治疗学》2016年第11期1209-1214,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(81260508);江西省"赣鄱英才555工程"人才资助计划;江西省教育厅科学技术研究项目(GJJ14227)

摘　　要：目的:研究柚皮素对MDR1 mRNA与P-糖蛋白(P-gp)表达的影响及其分子生物学机制。方法:将不同浓度的柚皮素(50、100、250、500μmol/L)单独或联合阿霉素(5μmol/L)作用于K562/A02细胞48 h,RT-PCR法检测MDR1 mRNA的表达水平,Western-blot法检测P-gp的表达水平,并以NF-κB抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)为对照,比较柚皮素与PDTC间的差异。结果:系列浓度柚皮素作用于K562/A02细胞48 h后能显著抑制MDR1 mRNA(IC_(50)=460.3μmol/L)及P-gp的表达(IC_(50)=286.3μmol/L),抑制作用随浓度的增加而增强;无毒剂量的柚皮素抑制强度与PDTC相近(P>0.05);经阿霉素诱导后二者抑制效应仍然相仿(P>0.05)。结论:柚皮素明显抑制K562/A02细胞MDR1 mRNA及P-gp的表达,可能与PDTC的作用机制相同,即限制IκB-α磷酸化,阻抑NF-κB的活化,从而抑制MDR1的转录,导致MDR1 mRNA及P-gp的表达量下调,最终使得药物外排转运效应下降。AIM： To study the influence of naringenin on the expression of MDR1 mRNA and P-gp and the molecular biological mechanisms. METHODS： K562/A02 cells were cultured with different concentrations of naringenin （50, 100, 250, 500 μmol/L） alone or in combination with adriamycin（5 μmol/L） for 48 h. The expression of MDR1 mRNA and P-gp in K562/A02 cells were detected by RT- PCR and Western-blot respectively. The difference between naringenin and PDTC were compared, while NF-κB specific inhibitor PDTC was used as positive control group. RESULTS： Naringenin inhibited the expression of MDR1 mRNA （IC50 =460.3 μmol/L） and P-gp （ ICs0 = 286.3μmol/L） significantly in K562/A02 cells cultured for 48 h, and the inhibi- tion enhanced with the increase of the drug concentration. The inhibition of non-toxic dose NG and PDTC were similar （ P 〉 0.05 ）, and still consistent after induced by ADM （ P 〉 0.05 ）. CONCLU- SION： Naringenin could inhibit the expression of MDR1 mRNA and P-gp in K562/A02 cells. The mechanisms may be that naringenin inhibits IκB-α phosphorylation and NF-κB activation, thus decrea- ses the transcription of MDR1, which leads to the down-regulation of MDR1 mRNA level and the ex- pression of P-gp, resulting in P-gp active declined at last.

关 键 词：柚皮素 K562/A02细胞 MDR1 MRNA P-糖蛋白 NF-ΚB 

分 类 号：R965.2[医药卫生—药理学]