南方医科大学学报2025，Vol.45Issue(4)：799-809,11.DOI:10.12122/j.issn.1673-4254.2025.04.15
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
Zheng Gan Decoction inhibits diethylnitrosamine-induced hepatocellular carcinoma in rats by activating the Hippo/YAP signaling pathway
摘要
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.关键词
正肝方/肝癌/Hippo/YAP通路/作用机制/二乙基亚硝胺Key words
Zheng Gan Decoction/hepatocellular carcinoma/Hippo/YAP pathway/therapeutic mechanism/diethylnitrosamine引用本文复制引用
宋添力,王一民,孙童,刘绪,黄胜,冉云..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[J].南方医科大学学报,2025,45(4):799-809,11.基金项目
国家自然科学基金地区基金(32160141) （32160141）
湖北省自然科学基金(2022CFB173) （2022CFB173）
湖北省教育厅科研项目(B2022101) （B2022101）
深圳市科技计划项目(JCYJ20220530172804010) （JCYJ20220530172804010）
