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牛蒡子苷元通过抑制PI3-K/Akt信号通路诱导肝癌细胞凋亡

王静泓 姜孝新 曾乐平 刘炼 周辉 刘玉冰

肿瘤药学Issue(6):430-435,6.
肿瘤药学Issue(6):430-435,6.DOI:10.3969/j.issn.2095-1264.2015.06.07

牛蒡子苷元通过抑制PI3-K/Akt信号通路诱导肝癌细胞凋亡

Arctigenin, a Natural Lignan Compound, Induces Apoptotic Death of Hepatocellular Carcinoma Cells via Suppression of PI3-K/Akt Signaling

王静泓 1姜孝新 1曾乐平 2刘炼 3周辉 3刘玉冰4

作者信息

  • 1. 南华大学附属第一医院,湖南衡阳,421001
  • 2. 中南大学基础医学院解剖学和神经生物学系,湖南长沙,410013
  • 3. 中南大学基础医学院解剖学和神经生物学系,湖南长沙,410013
  • 4. 中南大学湘雅医学院附属肿瘤医院,湖南长沙,410013
  • 折叠

摘要

Abstract

Objective To explore the effects of arctigenin, a natural lignan compound, on the growth of human hepatocellular carcinoma (HCC) cells and the possible mechanisms. Methods The HepG2 and Hep3B cells were treated with different concentrations of arctigenin. The MTT assay was applied to detect the cell proliferation of HCC cells. Flow cytometry was applied to detect the cell apoptosis and cell cy-cle, and Western blot was adopted to detect the expressions of caspase-3 and caspase-9 as well as the expressions of anti-apoptotic proteins in cells. Manipulating Akt signaling was used to determine its role in the action of arctigenin. Results Arctigenin significantly inhibited the proliferation and induce the apoptosis of HCC cells in a concentration-dependent manner. Arctigenin induced the activation of caspase-9 and caspase-3. Overexpression of a constitutively active Akt mutant blocked arctigenin-induced apoptosis. Combinational treatment with arctigenin and the PI3K inhibitor LY294002 enhanced apoptosis significantly. Arctigenin reduced the expression of Bcl-xL, Mcl-1 and sur-viving, and the phosphorylation of mTOR and S6K, which were significantly reversed by overexpression of constitutively-active Akt. Con-clusion Arctigenin could down-regulate the expressions of anti-apoptotic proteins and promote the apoptosis of hepatocellular carcinoma cells by inactivating PI3-K/Akt signaling.

关键词

牛蒡子苷元/原发性肝癌/细胞凋亡

Key words

Arctigenin/Hepatocellular carcinoma/Apoptosis

分类

医药卫生

引用本文复制引用

王静泓,姜孝新,曾乐平,刘炼,周辉,刘玉冰..牛蒡子苷元通过抑制PI3-K/Akt信号通路诱导肝癌细胞凋亡[J].肿瘤药学,2015,(6):430-435,6.

基金项目

湖南省自然基金资助项目(14JJ2092)。 ()

肿瘤药学

OACSTPCD

2095-1264

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