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体外抑制脂肪酸合酶通过下调 PI3K/Akt 信号通路抑制骨肉瘤细胞的侵袭和迁移。

Inhibition of fatty acid synthase suppresses osteosarcoma cell invasion and migration via downregulation of the PI3K/Akt signaling pathway in vitro.

机构信息

Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China.

出版信息

Mol Med Rep. 2013 Feb;7(2):608-12. doi: 10.3892/mmr.2012.1220. Epub 2012 Dec 3.

Abstract

In the present study, the effect of fatty acid synthase (FASN) inhibition on cell invasion and migration in vitro was investigated. A recombinant plasmid containing a microRNA targeting the FASN gene was used to inhibit FASN expression in U2‑OS cells. Cell migration and invasion were investigated using wound healing and Transwell invasion assays. We found that cell invasion and migration were suppressed by inhibiting FASN. In addition, the effect of inhibition of FASN on phosphorylation of Akt was investigated by detecting the expression levels of pAkt using western blot analysis. Furthermore, protein expression levels of nuclear factor‑κB (NF‑κB; p65) and matrix metalloproteinase (MMP)‑2 and ‑9 were also measured by western blot analysis. Results demonstrated that expression levels of pAkt, NF‑κB (p65) and MMP‑2 and ‑9 proteins were reduced significantly by inhibiting FASN. Therefore, we confirmed that inhibition of FASN by RNA interference suppresses osteosarcoma cell metastasis via downregulation of the phosphoinositide 3‑kinase/Akt/NF‑κB signaling pathway in vitro.

摘要

在本研究中,研究了脂肪酸合酶 (FASN) 抑制对体外细胞侵袭和迁移的影响。使用含有靶向 FASN 基因的 microRNA 的重组质粒来抑制 U2-OS 细胞中的 FASN 表达。使用划痕愈合和 Transwell 侵袭实验研究细胞迁移和侵袭。结果发现,抑制 FASN 可抑制细胞侵袭和迁移。此外,通过 Western blot 分析检测 pAkt 的表达水平来研究抑制 FASN 对 Akt 磷酸化的影响。此外,还通过 Western blot 分析测量核因子-κB (NF-κB; p65) 和基质金属蛋白酶 (MMP)-2 和 -9 的蛋白表达水平。结果表明,通过 RNA 干扰抑制 FASN 可显著降低 pAkt、NF-κB (p65) 和 MMP-2 和 -9 蛋白的表达水平。因此,我们证实通过抑制 FASN,体外通过下调磷酸肌醇 3-激酶/Akt/NF-κB 信号通路抑制骨肉瘤细胞转移。

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