Effect Of Kaempferol On The Expression Of MDR1 In HepG2 And CaCo2 Cells And It's Relationship With PXR

BACKGROUND: P-glucoprotein, which is encoded by MDR1, is the most important transporter in drug disposition. The phenomenon of multidrug resistance is associated with the over-expression of P-glucoprotein. As we all know, P-glucoprotein and CYP3A4 have the similar tissue distribution and a lot of same substates. Many inducer of CYP3A4 can induce the expression of P-glucoprotein simultaneously. It has been reported that kaempferol can induce CYP3A4 through PXR。AIMS: Our study is to investigate whether Kaemferol has effect on the expression of MDR1. Also we aim to find out whether PXR acts in this regulation.METHODS: We treated 0.00μM,0.01μM,0.1μM,1μM,5μM,10μM,20μM,50μM concentrations of kaempferol with HepG2 cells and CaCo2 cells respectively and measured the mRNA expression of MDR1 by Real-Time PCR: then we treated CaCo2 cells with 20μM kaempferol for different time to see if there exsist a time-dependent manner. We also construct PXR transient cotransfection report gene assay in HepG2 cells and CaCo2 cells, and treated 0.1μM,1μM,10μM,20μM,50μM concentrations of kaempferol with cells respectively, then we got the activity of MDR1 promoter by double luciferase detection.RESULTS: The results showed that when we treated HepG2 cells with 10μM,20μM and 50μM kaempferol for 24 hours, the mRNA expression of MDR1 increased significantly. After 5μM,10μM,20μM and 50μM kaempferol were added to CaCo2 cells respectively for 24 hours, the mRNA expression of MDR1 increased. When we treated CaCo2 cells with 20μM kaempferol for 12h,24h,48h respectively, the mRNA expression of MDR1 were significantly different between the kaempferol group and the vehicle control group. In the PXR transient cotransfection report gene assay, when we added kaempferol to transfected HepG2 and CaCo2 cells for 24 hours, there were no statistical significance between the kaempferol groups and the vehicle control group.CONCLUSIONS: Our results showed that kaempferol can induce the expression of MDR1 in cells. But the induction seemed not through the activiation of PXR.