Experimental evaluation of inhibitory effect of 10-hydroxycamptothecin on hypoxia-inducible factor-1alpha expression and angiogenesis in liver tumors after transcatheter arterial embolization.

摘要

PURPOSE: To evaluate the effect of transcatheter administration of 10-hydroxycamptothecin (HCPT), a hypoxia-inducible factor-1alpha (HIF-1alpha) inhibitor, on HIF-1alpha expression and angiogenesis in liver tumors after transcatheter arterial embolization in an animal model. MATERIALS AND METHODS: VX2 tumors were implanted in the livers of 30 rabbits. The animals were divided randomly into three groups of 10 animals each. Group 1 animals received hepatic intraarterial infusion of distilled water. Group 2 animals received iodized oil infusion followed by embolization with 150-250 mum of polyvinyl alcohol particles. Group 3 animals received infusion of a mixture of HCPT (1 mg/kg body weight) with iodized oil followed by the particle embolization. Six hours or 3 days after transcatheter treatment, the animals were sacrificed, and the tumor samples were harvested. Immunohistochemical staining was performed to evaluate the levels of HIF-1alpha and vascular endothelial growth factor (VEGF) protein as well as microvessel density. RESULTS: The levels of HIF-1alpha and VEGF and microvessel density in tumors of group 2 were significantly higher than those of group 1 or 3 (P < .05). However, no significant differences were noted in tumors between group 1 and 3 (P > .05). HIF-1alpha levels were significantly correlated with VEGF levels (r = .587, P = .001) and microvessel density (r = .527, P = .003). CONCLUSIONS: Transcatheter infusion of HCPT has an inhibitory effect on HIF-1alpha expression and angiogenesis in liver tumors after transcatheter arterial embolization.