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01-04-2020 | PRECLINICAL STUDIES

Emodin, a natural anthraquinone, suppresses liver cancer in vitro and in vivo by regulating VEGFR₂ and miR-34a

Authors: Jianguo Bai, Jianfei Wu, Ruifeng Tang, Chao Sun, Junwei Ji, Zhaolin Yin, Guangjun Ma, Wei Yang

Published in: Investigational New Drugs | Issue 2/2020

Summary

The pharmacokinetic (PK) and potential effects of Emodin on liver cancer were systematically evaluated in this study. Both the intragastric administration (i.g.) and hypodermic injection (i.h.) of Emodin exhibited a strong absorption (absorption rate < 1 h) and elimination capacity (t_1/2 ≈ 2 h). The tissue distribution of Emodin after i.h. was rapid and wide. The stability of Emodin in three species of liver microsomes wasrat >human> beagle dog. These PK data provided the basis for the subsequent animal experiments. In liver cancer patient tissues, the expression of vascular endothelial growth factor (VEGF)-induced signaling pathways, including phosphorylated VEGF receptor 2 (VEGFR₂), AKT, and ERK_1/2,were simultaneously elevated, but miR-34a expression was reduced and negatively correlated with SMAD₂ and SMAD₄. Emodin inhibited the expression of SMAD_2/4 in HepG2 cells by inducing the miR-34a level. Subsequently, BALB/c nude mice received a daily subcutaneous injection of HepG2 cells with or without Emodin treatment (1 mg/kg or 10 mg/kg), and Emodin inhibited tumorigenesis and reduced the mortality rate in a dose-dependent manner. In vivo experiments showed that cell proliferation, migration, and invasion were promoted by VEGF or miR-34a signal treatment but were inhibited when combined with Emodin treatment. All these results demonstrated that Emodin inhibited tumorigenesis in liver cancer by simultaneously inhibiting the VEGFR₂-AKT-ERK_1/2signaling pathway and promoting a miR-34a-mediated signaling pathway.

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Title: Emodin, a natural anthraquinone, suppresses liver cancer in vitro and in vivo by regulating VEGFR2 and miR-34a
Authors: Jianguo Bai
Jianfei Wu
Ruifeng Tang
Chao Sun
Junwei Ji
Zhaolin Yin
Guangjun Ma
Wei Yang
Publication date: 01-04-2020
Publisher: Springer US
Published in: Investigational New Drugs / Issue 2/2020
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00777-5

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