Fig. 2

Differential effects on cell proliferation and cell death of single and dual MET/PI3K inhibition in MET-driven models with and without PIK3CA mutations. a, cell proliferation was assessed after 72 h of treatment using a resazurin-reduction based assay. b, combination effects were estimated by calculating excess over the bliss. Bold-italic numbers indicate values significantly different to 0 according to one-sample t-test (=0 additivity, >0 effect more-than-additive, <0 less-than-additive). c, caspase-3 enzymatic activity was measured using a specific fluorogenic substrate after 72 h of treatment. Comparisons of single tepotinib treatment vs. combination treatment were significant in all cell lines: vector (p = 0.0451), E545K (p < 0.001), and H1047R (p = 0.004). d, representative images (20x magnification) of viable (calcium AM, green) and dead (ethidium homodimer, red) cells. Lower panel: percentage of dead cells in each treatment condition