Fig. 4
Co-inhibition of PLK1 and KRASG12C synergistically suppresses tumor growth and overcomes resistance in vivo. Relative tumor volumes (RTV) of KRASG12C-mutant MIA PaCa-2 (A), MIA PaCa-2-R (B) and SW1573 (C) cell xenografts treated with vehicle, MRTX849 (10 or 30 mg/kg/day), Volasertib (20 mg/kg/week), alone or in combination; statistical significance was evaluated by one-way ANOVA with Tukey’s multiple comparison test. *P < 0.05, **P < 0.01, and ***P < 0.001. Data are the mean ± SEM (5 mice/group). Tumors in each model were weighted at the end of the treatments. D–F Changes in tumor volumes of individual mice in MIA PaCa‑2 (D), MIA PaCa‑2-R (E) and SW1573 (F) xenografts at the end of treatment were calculated. G–I Mouse body weights in each model were measured every 3 days during the experiments. J Western blot analyses of the tumor tissues from the above xenografts. K IHC analyses of MIA PaCa-2 and SW1573 tumor tissues after the treatment. Scale bar, 50 μm. Cells positive for c-Myc and cleaved caspase-3 were quantified (n = 3). Data are shown as mean ± SD. Statistical significance was assessed using two-tailed unpaired Student’s t test. *P < 0.05, **P < 0.01, and ***P < 0.001