Fig. 12
Effect of metformin and CR plus chemo-immunotherapy in intramuscular K and KL tumors: Tumor growth inhibition in KRASG12D (A, B) and KRASG12D/LKB1del (C, D) intramuscularly injected in immunocompetent mice (N = 10). For five weeks metformin (MET) was administered daily at 300 mg/kg, cisplatin (DDP) 5 mg/kg once a week, anti PD-1 at 100 μg/dose twice a week, while the caloric restriction (CR) consisted of 36 h of fasting once a week. Two-way ANOVA was used for statistical analysis (**p < 0.01, ****p < 0.0001). Error bars indicate SEM. A, B Non statistically significant effects were observed in K tumours. For KL tumours, the most statistically significant results have been reported in panels C. D CR increases the effect of DDP/anti PD-1 combination (DDP/anti PD-1 vs DDP/anti PD-1/MET **p < 0.01) but (C, D) the best effect were reached with the DDP/anti PD-1/MET/CR combination