3.6 DXM inhibited OATP1B1 promoter activation via LXRα
In addition, the 5’ UTR of the OATP1B1 DNA containing the LXRα response
element was cloned into the pGL3 vector to assess the effect of DXM on
LXRα-mediated OATP1B1 promoter activation. The activity of the firefly
luciferase was monitored after incubation by 400 nM DXM or LXRα agonist
GW3965 as a positive control. As shown in Figure 6, the reporter
activity was increased by 74% in the GW3965 group (****P< 0.0001) and decreased by 33% in the DXM group (***P< 0.001) as compared with 0.1% DMSO negative control.
Meanwhile, compared with the GW3965 group, the DXM+GW3965 group also
reduced the reporter activity by about 27% (****P <
0.0001). Thus, these results suggested that the repressive effect of DXM
on the OATP1B1 expression was the result of the inhibition of OATP1B1
promoter activation via LXRα.