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Qianqian Qu, Zhongshun He, Yulei Jiang, Di Lu, Xiaolin Long, Yu Ding, Biao Xu, Xiaoqiong He
(Stomatology Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, China (mainland))
Med Sci Monit 2019; 25:7527-7537
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 C₁₈H₁₇NO₆ on osteosarcoma cells.
MATERIAL AND METHODS: Human MNNG osteosarcoma cells were treated with different concentrations of C₁₈H₁₇NO₆. 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: C₁₈H₁₇NO₆ inhibited MNNG proliferation in a dose- and time-dependent manner and inhibited MMP-2, MMP-9, and VEGF secretion. C₁₈H₁₇NO₆ treatment significantly downregulated N-cadherin and Vimentin expression levels and upregulated E-cadherin expression levels in vitro and in vivo. C₁₈H₁₇NO₆ inhibited tumor growth in a MNNG xenograft. We also found that C₁₈H₁₇NO₆ 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 C₁₈H₁₇NO₆. LY294002 (a PI3K inhibitor) downregulated p-PI3K and p-AKT could mimic the inhibitory effect of C₁₈H₁₇NO₆.
CONCLUSIONS: Our results suggest that C₁₈H₁₇NO₆ can inhibit human MNNG osteosarcoma cell invasion and migration via the PI3K/AKT signaling pathway both in vivo and in vitro. C₁₈H₁₇NO₆ may be a highly effective and low-toxicity natural drug for the prevention or treatment of OS.