Liposomal curcumin inhibits hypoxia-induced angiogenesis after transcatheter arterial embolization in VX2 rabbit liver tumors

摘要

Purpose: The purpose of the study is to investigate the inhibition of hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors by liposomal curcumin.Materials and methods: A total of 54 VX2 rabbits were divided into three groups, and each group had three subgroups according to the sacrifice time. The animals in the control group (n=18) underwent sham embolization. Transcatheter arterial embolization (TAE)-treated group (n=18) animals underwent embolization with lipiodol (0.1?mL/kg body weight) and 90–180?μm polyvinyl alcohol (PVA) particles. Liposomal curcumin TAE-treated group (n=18) animals underwent embolization with liposomal curcumin (20?mg/kg body weight) mixed with lipiodol (0.1 mL/kg body weight) and 90–180?μm PVA particles. After embolization, the animals in each subgroup were sacrificed at 6?hours, 24?hours, and 3?days, and the tumor samples were collected. Immunohistochemical staining was performed to evaluate expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins, and microvessel density (MVD). Real-time polymerase chain reaction was performed to examine VEGF mRNA levels.Results: The levels of HIF-1α and VEGF, and MVD in tumors of liposomal curcumin TAE-treated group were significantly decreased compared to the TAE-treated group (P0.05). The HIF-1α protein correlated considerably with VEGF mRNA (r=0.705, P=0.001) and protein (r=0.655, P=0.003), and MVD (r=0.521, P=0.027). A significant correlation between VEGF protein and MVD was noted as well (r=0.519, P=0.027).Conclusion: Liposomal curcumin downregulates HIF-1α protein levels and inhibits hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors.