Figure 5.

CDK2 inhibitor dinaciclib increases the expression and activity of PXR target genes. (A) Primary mouse hepatocytes were treated with dinaciclib (4 μM) for 24 h, and the gene expression was analyzed at mRNA levels. (B) Dinaciclib promoted the oxidative activity of CYP3A4. HepG2 cells were treated with dinaciclib (0, 1, 2 or 4 μM) for 24 h, and cell lysates were prepared and assayed for CYP3A4 activity. (C,D) Dinaciclib promoted the efflux activity of P-gp. HepG2 cells were treated with or without dinaciclib (4 μM) for 24 h, then incubated with DMEM (10% FBS) supplemented with 5 μg·mL⁻¹ Rho 123 for 30 min. The efflux activity of P-gp was analyzed immediately by flow cytometry (C) or observed under a fluorescence microscope (D). Scale bar: 50 μm. Experiments described in this figure were repeated independently at least three times, and data are expressed as mean ± SEM (n = 3). * p < 0.05 and ** p < 0.01 indicates significant difference compared with control group.