Stomatology Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, China (mainland).
Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, China (mainland).
Med Sci Monit. 2019 Oct 7;25:7527-7537. doi: 10.12659/MSM.918431.
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 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.
骨肉瘤（OS）是一种高度侵袭性、转移性骨肿瘤，预后不良，多见于儿童和青少年。因此，急需新的药物和治疗方法。本研究旨在探讨 C₁₈H₁₇NO₆ 对骨肉瘤细胞的作用及潜在机制。
用人 MNNG 骨肉瘤细胞，用不同浓度的 C₁₈H₁₇NO₆ 处理。通过 CCK-8 法检测 MNNG 细胞的增殖。通过划痕愈合试验和 Transwell 迁移和侵袭试验检测细胞迁移和侵袭。ELISA 法检测 MMP-2、MMP-9 和 VEGF 的分泌。最后，通过 Western blot 和 qRT-PCR 分别检测蛋白和 mRNA 的表达。
C₁₈H₁₇NO₆ 呈剂量和时间依赖性抑制 MNNG 增殖，并抑制 MMP-2、MMP-9 和 VEGF 的分泌。C₁₈H₁₇NO₆ 处理显著下调体外和体内 N-钙粘蛋白和波形蛋白的表达水平，上调 E-钙粘蛋白的表达水平。C₁₈H₁₇NO₆ 抑制 MNNG 异种移植瘤的生长。我们还发现，C₁₈H₁₇NO₆ 可以显著降低体内和体外 PI3K/AKT 信号通路的磷酸化。然而，740Y-P（一种 PI3K 激动剂）对 C₁₈H₁₇NO₆ 处理的 MNNG 细胞的增殖、迁移和侵袭有相反的影响。LY294002（一种 PI3K 抑制剂）下调 p-PI3K 和 p-AKT 可以模拟 C₁₈H₁₇NO₆ 的抑制作用。
我们的结果表明，C₁₈H₁₇NO₆ 可以通过体内和体外的 PI3K/AKT 信号通路抑制人 MNNG 骨肉瘤细胞的侵袭和迁移。C₁₈H₁₇NO₆ 可能是一种高效低毒的天然药物，可用于预防或治疗 OS。
