Oncotarget

Research Papers:

Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9

Mingyan He, Jiayun Hou, Lingyan Wang, Minghuan Zheng, Tingting Fang, Xiangdong Wang _ and Jinglin Xia

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Oncotarget. 2017; 8:42136-42148. https://doi.org/10.18632/oncotarget.15010

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Abstract

Mingyan He1,*, Jiayun Hou2,*, Lingyan Wang2,*, Minghuan Zheng2, Tingting Fang1, Xiangdong Wang2 and Jinglin Xia1,3

1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China

2Clinical Science Institute, Zhongshan Hospital, Fudan University, Shanghai, China

3Minhang Hospital, Fudan University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Jinglin Xia, email: xiajinglin@fudan.edu.cn

Xiangdong Wang, email: xianagdong.wang@clintransmed.org

Keywords: hepatocellular carcinoma, root of Actinidia chinensis, PCSK9, cholesterol metabolism

Received: September 09, 2016    Accepted: January 16, 2017    Published: February 02, 2017

ABSTRACT

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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