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N-反式阿魏酰章鱼胺通过AKT、p38丝裂原活化蛋白激酶和上皮-间质转化相关信号抑制肝癌细胞侵袭

Inhibition of invasion by N-trans-feruloyloctopamine via AKT, p38MAPK and EMT related signals in hepatocellular carcinoma cells.

作者信息

Bai Zhong-Tian, Wu Zheng-Rong, Xi Li-Li, Li Xun, Chen Peng, Wang Fu-Qiang, Meng Wen-Bo, Zhou Wen-Ce, Wu Xin-An, Yao Xiao-Jun, Zhang Min

机构信息

The Second Department of General Surgery, The First Hospital of Lanzhou University, Key Laboratory of Biotherapy and Regenerative Medicine, Gansu Province, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, Gansu, China.

School of Pharmacy, Lanzhou University, Lanzhou 730020, China.

出版信息

Bioorg Med Chem Lett. 2017 Feb 15;27(4):989-993. doi: 10.1016/j.bmcl.2016.12.073. Epub 2016 Dec 30.

Abstract

N-trans-feruloyloctopamine (FO) isolated from Garlic skin was identified as the primary antioxidant constituents, however, the effect of which on HCC invasion is still unclear. Herein, the FO was synthesized and its antitumor activities were evaluated in HCC cell lines. Cellular functional analyses have revealed that the reformed FO owns strong abilities of inhibiting cell proliferation and invasion in HCC cells. Molecular data have further showed that FO could significantly decrease the phosphorylation levels of Akt and p38 MAPK. In addition, the expression of Slug was inhibited and the level of E-cadherin increased. Molecular docking analysis indicates that the H-bond and hydrophobic interactions were critical for FO and E-cadherin binding, but FO did not seem to act directly on phosphorylated Akt and p38 MAPK. We have thus concluded that reformed FO inhibits cell invasion might be directly through EMT related signals (E-cadherin) and indirectly through PI3K/Akt, p38 MAPK signaling pathways. FO might be a promising drug in HCC treatment and prognosis.

摘要

从蒜皮中分离出的N-阿魏酰章鱼胺(FO)被确定为主要的抗氧化成分,然而,其对肝癌侵袭的影响仍不清楚。在此,合成了FO并在肝癌细胞系中评估了其抗肿瘤活性。细胞功能分析表明,改良后的FO具有很强的抑制肝癌细胞增殖和侵袭的能力。分子数据进一步表明,FO可显著降低Akt和p38 MAPK的磷酸化水平。此外,Slug的表达受到抑制,E-钙黏蛋白水平升高。分子对接分析表明,氢键和疏水相互作用对FO与E-钙黏蛋白的结合至关重要,但FO似乎并不直接作用于磷酸化的Akt和p38 MAPK。因此,我们得出结论,改良后的FO抑制细胞侵袭可能直接通过与上皮-间质转化相关的信号(E-钙黏蛋白),并间接通过PI3K/Akt、p38 MAPK信号通路。FO可能是肝癌治疗和预后方面一种有前景的药物。

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