Zheng Gan Decoction inhibits diethylnitrosamine-induced hepatocellular carcinoma in rats by activating the Hippo/YAP signaling pathway
10.12122/j.issn.1673-4254.2025.04.15
- VernacularTitle:正肝方对二乙基亚硝胺诱导的肝癌大鼠的抗癌作用及机制:基于激活Hippo/YAP通路
- Author:
Tianli SONG
1
;
Yimin WANG
;
Tong SUN
;
Xu LIU
;
Sheng HUANG
;
Yun RAN
Author Information
1. 湖北民族大学医学部,湖北 恩施 445000;湖北民族大学风湿性疾病发生与干预湖北省重点实验室,湖北 恩施 445000
- Publication Type:Journal Article
- Keywords:
Zheng Gan Decoction;
hepatocellular carcinoma;
Hippo/YAP pathway;
therapeutic mechanism;
diethylnitrosamine
- From:
Journal of Southern Medical University
2025;45(4):799-809
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of Zheng Gan Decoction(ZGF)on tumor progression in a rat model of diethylnitrosamine(DEN)-induced hepatocellular carcinoma(HCC)and explore the possible mechanism.Methods Seventy SD rats were subjected to regular intraperitoneal injections of DEN(50 mg/kg)for 12 weeks to induce HCC tumorigenesis,with another 10 rats receiving saline injections as the normal control.After successful modeling,the rats were randomized into 5 groups(n=10)for daily treatment with distilled water(model group),Huaier Granules(4 g/kg;positive control group),or ZGF at low,medium,and high doses(2,4,and 8 g/kg,respectively)via gavage for 17 weeks.Body weight changes of the rats were monitored,and after completion of the treatments,the rats were euthanized for measurement of liver,spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining.The expressions of YAP,p-YAP,MST1,LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting.Results Compared with the normal control rats,the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate,increased body weight and liver and spleen indices,and a lowered thymus index.ZGF treatment obviously reduced liver and spleen indices,increased the thymus index,and improved pathologies of the liver tissues of the rat models.Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats,which also exhibited significantly upregulated hepatic expressions of MST1,LATS1 and p-LATS1.Conclusion ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression,which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.
