Emodin suppresses hepatocellular carcinoma growth by regulating macrophage polarization via microRNA-26a/transforming growth factor beta 1/protein kinase B

Bioengineered

Xiansheng Zhao¹  Xuejiao Chen²  Jiao Yin²  Guanxin Shen³ 

[1] Department of Hepatology, Ningbo Huamei Hospital, University of Chinese Academy of Sciences, 175 Yongfeng Road, Ningbo, 315010, China;Department of Immunology, School of Basic Medicine, Hubei University of Arts and Science, 296 Longzhong Road, Xiangyang, 441053, China;Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China;

关键词: Hepatocellular carcinoma;    emodin;    macrophage polarization;    TGF-β1;    miR-26;   

DOI  :  10.1080/21655979.2022.2061295

来源: DOAJ

【 摘 要 】

Accumulating evidence has demonstrated that M2 macrophages contribute to the progression of hepatocellular carcinoma (HCC). Emodin is an anti-tumor agent and potentially regulates macrophage polarization. This study aims to explore the effect of emodin on M2 polarization in HCC and its underlying mechanism. After co-culture systems of M2 macrophages and HCC (HepG2 and Huh7) cells were established, it was shown that co-culture with M2 macrophages could promote both the proliferation and invasion of HepG2 and Huh7 cells. Emodin induces the transformation of M2 to M1 macrophages, thereby inhibiting the proliferation and invasion of HepG2 and Huh7 cells mediated by co-culturing with M2 macrophages. Based on bioinformatics analysis and in vitro validation, it was found that the effect of emodin on M2 polarization was regulated by the microRNA-26a (miR-26)/Transforming growth factor beta 1 (TGF-β1)/Protein kinase B (Akt) axis. In vivo analysis showed that co-culturing with M2 macrophages markedly facilitated the growth of HepG2 cells, which was significantly inhibited by emodin. Western blot analysis on xenografts confirmed that emodin could induce transformation of M2 to M1 macrophages and reverse the up-regulation of PCNA, TGF-β1, and p-Akt induced by M2 macrophages. In summary, our findings uncover a novel mechanism behind the anti-tumor effects of emodin that regulates M2 polarization via miR-26a/TGF-β1/Akt to suppress HCC growth.

【 授权许可】

Unknown