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

Abstract

Feng Dai,1,2 Xiuming Zhang,3 Wenrong Shen,3 Jun Chen,4 Liucheng Liu,5 Gejun Gao6 1The First College of Clinical Medicine, Nanjing University of Chinese Medicine, 2Department of Interventional Radiology, The Second Hospital of Nanjing, Medical School, Southeast University, 3Department of Radiology, 4Department of Interventional Radiology, Jiangsu Province Tumor Hospital, 5Department of Pharmacy, Jiangsu Aosakang Pharmaceutical Co. Ltd, 6Department of Radiology, Jiangsu Province Hospital of TCM, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China 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 (P<0.05). There was a slight decrease in tumor size in the liposomal curcumin TAE-treated group at third-day time points compared to the TAE-treated group; the difference was not statistically significant (P>0.05). 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.Keywords: hypoxia-inducible factor-1α, angiogenesis, embolization, liver tumor