Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy

This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P