Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-β pathway.
Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-β pathway.
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DOI：
10.3892/mmr.2014.2891
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发表时间：
2015-03
影响因子：
3.4
通讯作者：
Zhu R
中科院分区：
文献类型：
--
作者：
Liu B;Zhou W;Chen X;Xu F;Chen Y;Liu J;Zhang Q;Bao S;Chen N;Li M;Zhu R
二氢杨梅素（DHM）是一种黄酮类化合物，具有很强的抗肿瘤活性。在本研究中，它表明，DHM显着抑制小鼠肝癌Hepal-6细胞的增殖和诱导凋亡。转化生长因子β（TGF-β）被认为是一种主要的促纤维化细胞因子，因此是治疗肝脏疾病的药物的常见靶标。本研究旨在研究TGF-β是否参与DHM触发的细胞活力抑制和凋亡诱导。采用MTT法检测DHM处理后Hepal-6细胞的存活率。TGF-β信号传导由Smads介导，并且烟酰胺腺嘌呤二核苷酸磷酸氧化酶4（N 0X 4）是活性氧类ROS产生的关键调节剂。通过蛋白质印迹分析来评估TGF-β、Smad 3、磷酸化（p）-Smad 2/3和NOX 4蛋白表达水平。采用定量聚合酶链反应检测TGF-β和NOX 4基因表达水平。结果表明，DHM呈浓度依赖性下调TGF-β、Smad 3、p-Smad 2/3和NOX 4的表达。细胞计数分析表明，DHM也以浓度依赖性方式抑制Hepal-6细胞生长。DHM处理后TGF-β表达显著降低。总之，本研究的结果定义并支持DHM的新功能，表明其通过下调小鼠肝细胞癌Hepal-6细胞中TGF-β/Smad 3信号通路的ROS产生来诱导细胞凋亡。
Dihydromyricetin (DHM) is a flavonoid compound which possesses potent antitumor activity. In the present study, it was demonstrated that DHM significantly inhibited proliferation and induced apoptosis in mouse hepatocellular carcinoma Hepal-6 cells. Transforming growth factor β (TGF-β) is recognized as a major profibrogenic cytokine and is therefore a common target for drugs in the treatment of liver disease. The present study aimed to investigate whether TGF-β was involved in DHM-triggered cell-viability inhibition and apoptosis induction. An MTT assay was used to evaluate the viability of Hepal-6 cells following DHM treatment. TGF-β signalling is mediated by Smads and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a crucial regulator of reactive oxygen species ROS production. TGF-β, Smad3, phosphorylated (p)-Smad2/3 and NOX4 protein expression levels were evaluated by western blot analysis. TGF-β and NOX4 gene expression levels were determined by quantitative polymerase chain reaction. The results indicated that DHM downregulated TGF-β, Smad3, p-Smad2/3 and NOX4 in a concentration-dependent manner. A cell counting assay indicated that DHM also inhibited Hepal-6 cell growth in a concentration-dependent manner. TGF-β expression was significantly decreased following DHM treatment. In conclusion, the results of the present study defined and supported a novel function for DHM, indicating that it induced cell apoptosis by downregulating ROS production via the TGF-β/Smad3 signaling pathway in mouse hepatocellular carcinoma Hepal-6 cells.
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影响因子：
5.4
作者：
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