C(18)H(17)NO(6) Inhibits Invasion and Migration of Human MNNG Osteosarcoma Cells via the PI3K/AKT Signaling Pathway

BACKGROUND: Osteosarcoma (OS) is a highly aggressive, metastatic bone tumor with a poor prognosis, and occurs more commonly in children and adolescents. Therefore, new drugs and treatments are urgently needed. In this study, we investigated the effect and potential mechanisms of C(18)H(17)NO(6) on osteosarcoma cells. MATERIAL/METHODS: Human MNNG osteosarcoma cells were treated with different concentrations of C(18)H(17)NO(6). The proliferation of the MNNG cells was examined via CCK-8 assay. Cell migration and invasion were tested via wound-healing assay and Transwell migration and invasion assays. ELISA was used to detect MMP-2, MMP-9, and VEGF secretion. Finally, Western blotting and qRT-PCR were used to detect protein and mRNA expressions, respectively. RESULTS: C(18)H(17)NO(6) inhibited MNNG proliferation in a dose- and time-dependent manner and inhibited MMP-2, MMP-9, and VEGF secretion. C(18)H(17)NO(6) treatment significantly downregulated N-cadherin and Vimentin expression levels and upregulated E-cadherin expression levels in vitro and in vivo. C(18)H(17)NO(6) inhibited tumor growth in a MNNG xenograft. We also found that C(18)H(17)NO(6) can significantly reduce the phosphorylation of the PI3K/AKT signaling pathway in vivo and in vitro. However, 740Y-P (a PI3K agonist) had the opposite effect on proliferation, migration and invasion of MNNG cells treated with C(18)H(17)NO(6). LY294002 (a PI3K inhibitor) downregulated p-PI3K and p-AKT could mimic the inhibitory effect of C(18)H(17)NO(6). CONCLUSIONS: Our results suggest that C(18)H(17)NO(6) can inhibit human MNNG osteosarcoma cell invasion and migration via the PI3K/AKT signaling pathway both in vivo and in vitro. C(18)H(17)NO(6) may be a highly effective and low-toxicity natural drug for the prevention or treatment of OS.