Curcumin suppresses vasculogenic mimicry capacity of hepatocellular carcinoma cells through STAT3 and PI3K/AKT inhibition

Abstract

Background: Vasculogenic mimicry (VM) refers to the process in which highly invasive cancer cells mimic endothelial cells by forming blood channels. In the present study, we investigated the effect of curcumin, a natural product from turmeric, on VM of SK-Hep-1 human hepatocellular carcinoma (HCC) cells. Materials and Methods: In vitro VM, cell migration, and matrix metalloproteinase-9 (MMP9) production of HCC cells were determined by Matrigel tube formation assay, Transwell cell migration assay, and gelatin zymography, respectively. Effects of curcumin on AKT, signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK) and nuclear factor-Κ B (NF- Κ B) signaling pathways were determined by immunoblot analysis. Results: At non-cytotoxic concentrations, curcumin inhibited VM, reduced cell migration and MMP9 production of the HCC cells. Further study revealed that the anti-VM effect of curcumin was due to inhibition of AKT and STAT3 phosphorylation, as confirmed by specific inhibitors. Conclusion: Curcumin presents proven potential as an anti-VM agent in HCC cells, through down-regulation of STAT3 and AKT signaling pathways.