The first part of this study was to assess and compare fifteen widely used tumour models to select the ones most suitable for angiogenesis research. Two tumours were selected: a lung tumour (Lewis lung carcinoma, LLC) for its high vascularization and a colon carcinoma (colon tumour 26, C26) because it expresses both integrin αvβ3 and E-selectin. CT26 tumours were implanted subcutaneously (s.c.) in Balb/c mice for the ectopic model, or into the caecum for the orthotopic model. Tumours were evaluated by histology, spectrofluorescence, bioluminescence (BLI), magnetic resonance imaging (MRI) and ultrasound imaging (US). BLI was found to be more appropriate for early tumour detection, whereas MRI and US afforded excellent non invasive imaging techniques to accurately follow tumour growth of both ectopic and orthotopic tumour models. These models were very useful to investigate antiangiogenic therapies, in particular during the preclinical development of fisetin as an antiangiogenic agent. The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has been shown to possess antiangiogenic and anticancer properties. Because of the limited water solubility of fisetin, our aim was to design and optimize a liposomal formulation that could facilitate its in vivo administration. Low dose of liposomal fisetin (21 mg/kg) improved fisetin antitumoral activity in LLC tumor bearing mice compared to the administration of free fisetin. This liposomal formulation could therefore advantageously be employed to improve the antiangiogenic and anticancer activities of this flavonoid, as well as other flavonoids sharing similar problems of in vivo administration
Characterization of murine tumor models and their application in anti-angiogenic targeted therapies