Abstract
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&sub1;₈H&sub1;₇NO₆ on osteosarcoma cells. MATERIAL AND METHODS Human MNNG osteosarcoma cells were treated with different concentrations of C&sub1;₈H&sub1;₇NO₆. 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&sub1;₈H&sub1;₇NO₆ inhibited MNNG proliferation in a dose- and time-dependent manner and inhibited MMP-2, MMP-9, and VEGF secretion. C&sub1;₈H&sub1;₇NO₆ treatment significantly downregulated N-cadherin and Vimentin expression levels and upregulated E-cadherin expression levels in vitro and in vivo. C&sub1;₈H&sub1;₇NO₆ inhibited tumor growth in a MNNG xenograft. We also found that C&sub1;₈H&sub1;₇NO₆ 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&sub1;₈H&sub1;₇NO₆. LY294002 (a PI3K inhibitor) downregulated p-PI3K and p-AKT could mimic the inhibitory effect of C&sub1;₈H&sub1;₇NO₆. CONCLUSIONS Our results suggest that C&sub1;₈H&sub1;₇NO₆ can inhibit human MNNG osteosarcoma cell invasion and migration via the PI3K/AKT signaling pathway both in vivo and in vitro. C&sub1;₈H&sub1;₇NO₆ may be a highly effective and low-toxicity natural drug for the prevention or treatment of OS.