Transcriptional Regulation of CYP3A4/2B6/2C9 Mediated via Nuclear Receptor PXR by Helicid and Its Metabolites.

摘要: Objective. This study aims at establishing and validating an in vitro system to screen drug inducers of CYPs mediated via hPXR, as well studying transcriptional regulation hPXR by helicid its two metabolites. Methods. Cloning the nuclear receptor promoters CYP3A4, CYP2B6, CYP2C9, inserting trans-element upstream firefly luciferase reporter gene pGL4.17 vectors, then cotransfecting report vectors expression plasmid HepG2 cell line. After 24 hours, transfected cells were treated with (0.004, 0.04, 0.4 μmol/L) metabolite I II (0.0004, 0.004, 0.04 μmol/L) for 48 h, while rifampin (10 μmol/L) was included positive control 0.1% DMSO negative group. Cells lysized activity determined using a dual assay kit. Results. Helicid metabolites did not significantly increase promoter activities CYP2C9 PXR (). Conclusion. PXR-expressed platforms successfully established, I, do induce transcription CYP2C9.