Figure 5

Targeting cMET with INC280in vivo. A) cMET inhibition significantly impaired tumour growth in the orthotopic xenogeneic tumour model using L3.6pl human pancreatic cancer cell line. Increasing the dose to 20 mg/kg/d did not improve growth-inhibitory effects (*P < 0.05). B) Similar growth inhibition was observed in the orthotopic syngeneic model with murine Panc02 cells (*P < 0.05). C) In the subcutaneous syngeneic tumour model, treatment with gemcitabine (50 and 100 mg/kg twice/week) led to a transient deceleration of tumour growth, however, even when gemcitabine therapy was continued, tumours soon reentered the exponential growth phase. D) Expression of cMET in tumours treated with gemcitabine (100 mg/kg twice/week) was markedly increased as compared to untreated controls. E) INC280 and gemcitabine led to significant inhibition of tumour growth in the orthotopic syngeneic model (*P < 0.05 vs. control). Combination of both substances substantially enhanced this effect (^#P < 0.01 vs. control and ^#P < 0.05 vs. gemcitabine and INC280 alone). F) INC280 and gemcitabine significantly reduced tumour cell proliferation (Ki67) in vivo. Combination of both substances further increased the anti-proliferative capacity (^#P < 0.01 vs. control and ^#P < 0.05 vs. gemcitabine and INC280 alone). G) Significant reduction of tumour angiogenesis was observed upon either single agent or combination therapy, as determined by CD31 positive vessel area (*P < 0.05 vs. control). H) No effect on tumour cell apoptosis was detected by TUNEL staining.