Background: Hypoxia may affect the therapeutic efficacy of transcatheter arterial embolization (TAE), which is widely used in nonsurgical hepatocellular carcinoma (HCC). Liposomal curcumin can exert anticancer effect. Our purpose is to explore the antitumor effect of liposomal curcumin on the HCC after TAE.
Methods: The HepG2 cells were cultured under hypoxic condition (1% O2) and then treated with curcumin liposome. Cell viability, apoptosis and cell cycle were respectively measured by CCK-8 and a flow cytometry. The VX2 rabbits were randomly distributed into three groups: control group with saline embolization, TAE group with lipiodol embolization and curcumin liposome group with curcumin liposome and lipiodol embolization. MRI and CT perfusion scanning were performed after embolization. The hepatocyte apoptosis was measured by the terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL). The vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured by immunohistochemical. RT-PCR and Western blot were performed to examine mRNA and protein levels.
Results: By regulating the apoptosis-related molecules, curcumin liposome obviously inhibited the cell viability and promoted the apoptosis in G1 phase. Curcumin liposome reduced the tumor size and alleviated neoplasia in VX2 rabbits. Curcumin liposome decreased the expressions of MVD and VEGF and increased the apoptosis of liver tissues. The levels of hypoxia-inducible factor-1α (HIF-1α) and survivin were suppressed by curcumin liposome both in hypoxic cells and liver tissues in the VX2 rabbits.
Conclusion: Curcumin liposome exerted antitumor effect by regulating the proliferation- and apoptosis-related molecules. Curcumin liposome suppressed the HIF-1α and survivin levels and inhibited the angiogenesis in VX2 rabbits after TAE.
Keywords: HIF-1α; TAE; angiogenesis; antitumor; curcumin liposome; hypoxia; liver tumor.