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

Abstract

PurposeThe 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 methodsA 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.ResultsThe 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).ConclusionLiposomal curcumin downregulates HIF-1α protein levels and inhibits hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors.

Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors

“…A VX2 liver tumor rabbit model was established as previously described [ 38 ]. All VX2 rabbits were fed for 18-24 days after a VX2 tumor was implanted and examined with computed tomography scanning.…”

Curcumin in the treatment of liver cancer: From mechanisms of action to nanoformulations

“…Dai et al assessed the inhibitory effects of liposomal CUR on hypoxia‐induced angiogenesis in VX2 rabbit liver tumors. Although the administration of 20 mg/kg body weight liposomal CUR significantly decreased the levels of hypoxia‐inducible factor‐1α (HIF‐1α), VEGF, and tumor microvascular density (MVD), the tumor size reduction was not statistically significant compared with transcatheter arterial embolization (TAE)‐received group (F. Dai et al, 2015). HIF‐1α is a transcriptional factor that increases tumor angiogenesis by upregulating VEGF expression (Goradel et al, 2017).…”

Rational design of temperature-sensitive blood-vessel-embolic nanogels for improving hypoxic tumor microenvironment after transcatheter arterial embolization

“…In the present work, complex dispersions of PIB nanogels and iohexol were further optimized to address the problem of increasing viscosity caused by mixing with iohexol 35-38. The reduction of flowability may contribute to the hypoxic microenvironment (HIF-1α, VEGF, etc) of tumors 39-42. The temperature-sensitive sol-gel phase transition and rheological properties of the improved complex dispersions (PIBI-2240) were compared to those of Lipiodol, Ivalon, and original dispersions (PIBI-6150) 43.…”