MDM2 antagonists synergize with a MEK inhibitor in p53 wild-type cells. (A) Isobolograms showing the synergistic effect of RG7388 and HDM201 with GSK112021B in p53 wild-type cells (IB115 and IB111). Effect of GSK112021B, RG7388, and HDM201, alone or in combination, on apoptosis in p53 wild-type cells (IB115 and IB111) (B) and p53-null cells (IB136 and IB112) (C) Effect of GSK112021B, RG7388, and HDM201, alone or in combination, on cell cycle in p53 wild-type cells (IB115 and IB111) (D) and p53-null cells (IB136 and IB112) (E) * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001, and ns (non-significant). Data shown represent the results of three independent experiments.