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基于核磁共振代谢组学的大黄素对 HepG2 细胞的抗癌作用研究

Anti-Cancer Effects of Emodin on HepG2 Cells as Revealed by H NMR Based Metabolic Profiling.

机构信息

Center for Molecular Metabolism, School of Environmental and Biological Engineering , Nanjing University of Science and Technology , 200 Xiao Ling Wei Street , Nanjing 210094 , People's Republic of China.

出版信息

J Proteome Res. 2018 May 4;17(5):1943-1952. doi: 10.1021/acs.jproteome.8b00029. Epub 2018 Apr 26.

DOI:10.1021/acs.jproteome.8b00029
PMID:29676152
Abstract

Hepatic carcinoma is one of the most common cancers in the world, with a high incidence. Emodin is an anthraquinone derived from Polygonum multiflorum Thunb, possessing anti-cancer activity. The purpose of this study is to investigate the anti-cancer effect of different dosages of emodin on HepG2 cells using a H NMR based metabolic approach complemented with qRT-PCR and flow cytometry to identify potential markers and discover the targets to explore the underlying mechanism. Emodin can dose-dependently inhibit the growth of HepG2 cells, perturb cell cycle progression, down-regulate the expression of genes and proteins related to glycolysis, and trigger intracellular ROS generation. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) and correlation network analysis of the H NMR data showed significant changes in many endogenous metabolites after emodin exposure concerning oxidative stress and disturbances in amino acid and energy metabolism. These findings are helpful to understand the anti-cancer mechanism of emodin and provide a theoretical basis for its future application and development.

摘要

肝癌是世界上最常见的癌症之一,发病率较高。大黄素是从何首乌中提取的一种蒽醌类化合物,具有抗癌活性。本研究旨在采用基于 H NMR 的代谢组学方法,结合 qRT-PCR 和流式细胞术,研究不同剂量大黄素对 HepG2 细胞的抗癌作用,以鉴定潜在的标志物并发现靶点,探讨其潜在的作用机制。大黄素能剂量依赖性地抑制 HepG2 细胞的生长,扰乱细胞周期进程,下调与糖酵解相关的基因和蛋白表达,并引发细胞内 ROS 的产生。基于正交信号校正偏最小二乘判别分析(OSC-PLS-DA)和 H NMR 数据的相关网络分析显示,大黄素处理后,许多内源性代谢物与氧化应激和氨基酸及能量代谢紊乱有关,发生了显著变化。这些发现有助于理解大黄素的抗癌机制,并为其未来的应用和发展提供理论依据。

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