豆腐果苷对人孕烷X受体介导的CYP3A4和MDR1的转录调节作用

Transcriptional regulation of CYP3A4 and MDR1 mediated via nuclear receptor PXR by helicid

目的:建立和验证人孕烷X受体(human pregnant X receptor,hPXR)介导的CYP3A4、MDR1药物诱导剂的体外筛选体系,考察豆腐果苷对hPXR介导的CYP3A4、MDR1的转录调节作用。方法:利用构建的双荧光素酶报告基因系统,将表达载体和报告载体共转染HepG2细胞,以10μmol/L利福平为阳性对照,用不同浓度(0.004、0.04、0.4μmol/L)豆腐果苷处理48h后裂解细胞进行双荧光素酶活性检测。结果:不同浓度的豆腐果苷均不能通过激活hPXR来介导CYP3A4和MDR1表达上调,各浓度处理组的双荧光素酶比活性值与DMSO溶媒组差异无统计学意义(P>0.05)。结论:成功构建了hPXR介导的CYP3A4和MDR1药物诱导剂的体外筛选体系,并发现豆腐果苷不能通过激活hPXR介导CYP3A4和MDR1的表达上调。

AIM:To establish nuclear receptor PXR-expressed CYP3A4 and MDR1 dual luciferase reporter gene platform,and analyze the effect of helicid on hPXR-mediated transcriptional regulation of CYP3A4 and MDR1 genes.METHODS:PXR expression plasmid and reporter gene plasmid of either CYP3A4 or MDR1 were constructed based upon the dual luciferase reporter gene platform,and co-transfected to HepG2 cells.The transfected cells were treated with helicid of various concentrations(0.004,0.04 and 0.4 μmol/L)for 48 hours while ...