Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis

Cancer Cell International

Research

Zhixing Hu¹  Xiangying Yan¹  Congchong Li¹  Chu Zhang¹  Ya Lin¹  Yanqiong Zhang²  Yudong Liu³  Na Lin³  Tengteng Xu³  Xia Mao³ 

[1] College of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Qiuyang Road, Shangjie Town, Minhou County, 350122, Fuzhou, China;College of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Qiuyang Road, Shangjie Town, Minhou County, 350122, Fuzhou, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, 100700, Beijing, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, 100700, Beijing, China;

关键词: Hepatocellular carcinoma;    Pien-Tze-Huang;    Ferroptosis;    Solute carrier family 7 member 11;    Glutathione;    Glutathione peroxidase 4;   

DOI  :  10.1186/s12935-023-02946-2

 received in 2023-01-17, accepted in 2023-05-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMalignant transformation from hepatic fibrosis to carcinogenesis may be a therapeutic target for hepatocellular carcinoma (HCC). The aim of this study was to evaluate anti-cancer efficacy of Pien-Tze-Huang (PZH), and to investigate the underlying mechanisms by integrating transcriptional regulatory network analysis and experimental validation.MethodsA diethylnitrosamine (DEN)-induced HCC model in rats was established and used to evaluate the anti-cancer efficacy of PZH. After detecting a transcriptomic profiling, the “disease-related gene–drug effective target” interaction network was constructed, and the candidate targets of PZH against malignant transformation from hepatic fibrosis to HCC were identified and verified in vitro.ResultsPZH effectively alleviated the pathological changes of hepatic fibrosis and cirrhosis, and inhibited tumor formation and growth in DEN-induced HCC rats. Additionally, the administration of PZH reduced the levels of various hepatic function-related serological indicators significantly. Mechanically, a ferroptosis-related SLC7A11-GSH-GPX4 axis might be one of potential targets of PZH against malignant transformation from hepatic fibrosis to HCC. Especially, high SLC7A11 expression may be associated with poor prognosis of HCC patients. Experimentally, the administration of PZH markedly increased the trivalent iron and ferrous ion, suppressed the expression levels of SLC7A11 and GPX4 proteins, and reduced the GSH/GSSG ratio in the liver tissues of DEN-induced HCC rats.ConclusionsOur data offer an evidence that PZH may effectively improve the hepatic fibrosis microenvironment and prevent the occurrence of HCC through promoting ferroptosis in tumor cells via inhibiting the SLC7A11-GSH-GPX4 axis, implying that PZH may be a potential candidate drug for prevention and treatment of HCC at an early stage.

【 授权许可】

CC BY   
© The Author(s) 2023

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