Wnt/β-catenin signaling pathway may regulate the expression of angiogenic growth factors in hepatocellular carcinoma

Abstract

The Wnt/β-catenin signaling pathway plays a key role during hepatocellular carcinoma (HCC) genesis and development. The present study aimed to investigate the effects of the Wnt/β-catenin signaling pathway on the expression of angiogenic growth factors involved in HCC. The HCC HepG2 cell line was transfected with small interfering RNA (siRNA) against β-catenin. After 72 and 96 h, protein was extracted and the expression levels of β-catenin, matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF)-A, VEGF-C and basic fibroblast growth factor (bFGF) were detected by western blot analysis. β-catenin protein expression was inhibited at both time points. Notably, MMP-2, MMP-9, VEGF-A, VEGF-C and bFGF protein expression levels decreased at 72 h and then increased at 96 h after transfection. Our results demonstrated that in HCC cells, the Wnt/β-catenin signaling pathway may regulate the protein expression of the angiogenic factors, MMP-2, MMP-9, VEGF-A, VEGF-C and bFGF. These proteins were downstream of β-catenin signaling and were also regulated by other factors. In conclusion, the Wnt/β-catenin signaling pathway may contribute to the regulation of HCC angiogenesis, infiltration and metastasis through regulating the expression of these angiogenic factors.

Keywords: RNA interference; angiogenesis factor; hepatocellular carcinoma; signaling pathway; β-catenin.

Figure 1

Expression of β-catenin, MMP-2, MMP-9 and β-actin after knockdown of β-catenin by small interfering RNA transfection in hepatocellular carcinoma HepG2 cells. (A) Western blotting of the protein expression in the control group (1), 72 h after transfection (2) and 96 h after transfection (3). (B) Protein expression in the control group (1), 72 h after transfection (2) and 96 h after transfection (3). Y-axis is the quantitative results of gray-scale analysis. MMP, matrix metalloproteinase.

Figure 2

Expression of VEGF-A, VEGF-C, bFGF and β-actin after knockdown of β-catenin by small interfering RNA transfection in hepatocellular carcinoma HepG2 cells. (A) Western blotting of the protein expression in the control group (1), 72 h after transfection (2) and 96 h after transfection (3). (B) Protein expression levels in the control group (1), 72 h after transfection (2) and 96 h after transfection (3). Y-axis is the quantitative results of gray-scale analysis. VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor.