Experimental Evaluation of Inhibitory Effect of 10-Hydroxycamptothecin on Hypoxia-inducible Factor-1α Expression and Angiogenesis in Liver Tumors after Transcatheter Arterial Embolization

Abstract

To evaluate the effect of transcatheter administration of 10-hydroxycamptothecin (HCPT), a hypoxia-inducible factor-1α (HIF-1α) inhibitor, on HIF-1α expression and angiogenesis in liver tumors after transcatheter arterial embolization in an animal model. 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 μm 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-1α and vascular endothelial growth factor (VEGF) protein as well as microvessel density. The levels of HIF-1α 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-1α levels were significantly correlated with VEGF levels (r = .587, P = .001) and microvessel density (r = .527, P = .003). Transcatheter infusion of HCPT has an inhibitory effect on HIF-1α expression and angiogenesis in liver tumors after transcatheter arterial embolization.