Figure 4.

At the protein level, MDM2 inhibitors activate the p53-p21 pathway in hypoxic p53^WT cancer cells. The levels of HIF-1α, p53 and p21 levels were visualized after 24 h treatment with DMSO, nutlin-3a and navtemadlin (abbreviated navtem in figure) in either normoxia or hypoxia. Human cells (HCT116 and MCF7) were treated with 2 µM nutlin-3a or 0.5 µM navtemadlin, while mouse cells (B16-F10) were treated with 10 µM nutlin-3a or 2 µM navtemadlin. Whole membranes from two independent experiments were sequentially blotted using antibodies against each protein. Images of immunoblots and total protein levels (loading control) are cropped from whole blots; full-length blots are shown in SI Figs. 2–5.