Figure 4. Phenformin preferentially inhibits LKB1-deficient lung tumors in vivo.

(A) Representative ventral view images of bioluminescence from K_luc, KL_luc and KP_luc mice. Bioluminescence imaging (BLI) performed on K_luc (veh n=11, phen n=12 mice), KL_luc (veh n=10, phen n=10 mice) and KP_luc (veh n=7, phen n=7 mice) following three weeks of treatment with vehicle (water) or phenformin via ad lib feeding.

(B) Average BLI for each treatment group of the K_luc, KL_luc and KP_luc mice at three weeks treatment.

(C) Representative images of tumor burden in K_luc, KL_luc and KP_luc mice as shown by H&E stained lung sections (top panel) or the same images tissue segmented and pseudo-colored with Inform software (bottom panel). Scale bar = 1 mm.

(D) Box plots representing the mean tumor burden following 3 weeks of treatment. Tumor burden was calculated by averaging the red pseudocolored tumor area from H&E stained whole lung sections shown in (C) bottom panel.

(E) Representative images of H&E, Ki67 or TUNEL stained K_luc, KL_luc and KP_luc lung tumor sections. Ki67 or TUNEL positively stained cells (in green) and nuclei (in blue). Scale bar = 100 μm.

(F, G) Box plots representing the mean Ki67 (F) and TUNEL scores (G) from K_luc, KL_luc and KP_luc mice treated with vehicle or phenformin. (*) Statistical significance (p-value < 0.05) calculated using a non-parametric one-way ANOVA (Tukey test).

All data are represented as the mean ± SEM.