Abstract: Abstract: Objective To investigate the inhibitory effects and mechanism of ginsenoside Rg3 on vasculogenic mimicry of human breast cancer MCF-7 cell line. Methods The MCF-7 cells at logarithmic growth phase were obtained, and were cultured with different concentrations (0, 20, 50, 100, 150 and 300 mg/L) of ginsenoside Rg3. Cells cultured without Rg3 were served as controls. The IC50 were determined by CCK8 assay and anti-angiogenic effects were performed for testing the potential of tube-like structure (TLSs) formation. The expression levels of VEGF-A, MMP9 and HIF-1α were detected by Western blotting and real-time PCR. The secreted contents of VEGF-A and MMP9 were detected by enzyme linked immunosorbent assay (ELISA). Results The ginsenoside Rg3 suppressed the proliferation of MCF-7 cells in a dosedependent manner, in which IC50 was (115.34±8.50) mg/L. The formation numbers of TLSs in MCF-7 cells were significantly inhibited by Rg3 in concentration dependent manner in 50 mg/L, 100 mg/L and 150 mg/L for (19.0±1.0), (15.0±1.5), and (10.0±1.7) vs. controls (22.0±1.8, F=150.805, P < 0.05). The mRNA and protein expression levels of VEGF-A, MMP9 and HIF-1α protein were inhibited by 50 mg/L,100 mg/L and 150 mg/L Rg3 vs. controls (P < 0.05). Meanwhile, the contents of VEGF-A in MCF-7 cell supernatant was down-regulated by 50 mg/L,100 mg/L and 150 mg/L Rg3 vs. controls (P < 0.05). The contents of MMP-9 in MCF-7 cell supernatant was down-regulated by 100 mg/L and 150 mg/L Rg3 vs. controls (P < 0.05). There was no significant difference in MMP- 9 expression between 50 mg/L group and control group. Conclusion The ginsenoside Rg3 is able to inhibit the vasculogenic mimicry of MCF- 7 cells, which may be related with the down-regulation of VEGF-A, MMP9 and HIF-1α.

Key words:  breast neoplasms, vascular endothelial growth factor A, matrix metalloproteinase 9, hypoxia inducible factor-1α, michigan cancer foundation-7 cell, vasuclogenic mimicry, ginsenoside Rg3