Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9.
Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9.
复制标题
中华猕猴桃根提取物通过上调 PCSK9 抑制肝细胞癌中的胆固醇代谢。
DOI：
10.18632/oncotarget.15010
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发表时间：
2017-06-27
期刊：
影响因子：
--
通讯作者：
Xia J
中科院分区：
文献类型：
--
作者：
He M;Hou J;Wang L;Zheng M;Fang T;Wang X;Xia J
中华猕猴桃根提取物（Actinidia chinensis Planch root extract，acRoots）是一种具有抗肿瘤功效的中药。为了研究这种活性的机制，我们研究了acRoots对肝细胞癌（HCC）胆固醇代谢的影响。利用mRNA芯片分析鉴定acRoots调控的代谢相关基因。通过测定细胞内胆固醇水平和3，3 ′-双十八烷基吲哚羰花青标记的低密度脂蛋白（Dil-LDL）摄取来评价acRoots对胆固醇合成和摄取的影响。采用定量逆转录PCR、蛋白质印迹和流式细胞术分析代谢基因的表达。acRoots在5 mg/mL时降低LM 3和HepG 2细胞的活力，在30 mg/mL时降低HL-7702细胞的活力。基因表达谱显示，acRoots治疗改变了参与免疫反应、炎症、增殖、细胞周期控制和代谢的基因的表达。我们还证实acRoots增强了PCSK 9的表达，这对胆固醇代谢很重要。这导致LDL受体表达降低、LM 3细胞LDL摄取抑制、细胞内总胆固醇降低和增殖降低。这些作用通过PCSK 9过表达促进，并通过PCSK 9敲低拯救。我们的数据表明，acRoots是一种新型的抗肿瘤药物，通过PCSK 9介导的信号通路抑制胆固醇代谢。
Actinidia chinensis Planch root extract (acRoots) is a traditional Chinese medicine with anti-tumor efficacy. To investigate the mechanisms responsible for this activity, we examined the effects of acRoots on cholesterol metabolism in hepatocellular carcinoma (HCC). mRNA chip analysis was used to identify the metabolic genes regulated by acRoots. The effects of acRoots on cholesterol synthesis and uptake were evaluated by measuring intracellular cholesterol levels and 3,3′-dioctadecylindocarbocyanine-labeled low-density lipoprotein (Dil-LDL) uptake. Expression of metabolic genes was analyzed using quantitative reverse transcription PCR, western blotting, and flow cytometry. acRoots reduced the viability of LM3 and HepG2 cells at 5 mg/mL and HL-7702 cells at 30 mg/mL. Gene expression profiling revealed that treatment with acRoots altered expression of genes involved in immune responses, inflammation, proliferation, cell cycle control, and metabolism. We also confirmed that acRoots enhances expression of PCSK9, which is important for cholesterol metabolism. This resulted in decreased LDL receptor expression, inhibition of LDL uptake by LM3 cells, decreased total intracellular cholesterol, and reduced proliferation. These effects were promoted by PCSK9 overexpression and rescued by PCSK9 knockdown. Our data demonstrate that acRoots is a novel anti-tumor agent that inhibits cholesterol metabolism though a PCSK9-mediated signaling pathway.
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DOI：
10.1038/nrm3772
发表时间：
2014-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1038/nrgastro.2013.143
发表时间：
2014-01
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
6.5
作者：
Dong, Bin;Wu, Minhao;Liu, Jingwen
通讯作者：
Liu, Jingwen
影响因子：
4.8
作者：
Park, SW;Moon, YA;Horton, JD
通讯作者：
Horton, JD