Diwu Yanggan capcules alleviate hepatocellular carcinoma progression by regulating YAP signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE297952 | GEO | 2025/12/31
REPOSITORIES: GEO
Dataset's files
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Project description:Background: Hepatocellular carcinoma (HCC) is increasing in incidence and treatment is often unsuccessful. Thus, prevention in high-risk patients with established cirrhosis has been proposed as an alternative strategy. It has been suggested that the increased inflammation and fibrogenesis observed during cirrhosis predisposes the liver to future malignant transformation to HCC through a “field effect”. A growing body of evidence indicates that the green tea polyphenol, (-)-epigallocatechin gallate (EGCG), can reduce inflammation and fibrogenesis during chronic liver injury. Here, we test the hypothesis that EGCG administered in the setting of cirrhosis can prevent future HCC development. Methods: A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the efficacy of EGCG for inhibition of HCC formation in these cirrhotic livers. DEN (50 mg/kg) was administered weekly throughout the study while 0.02% EGCG was given in drinking water beginning at the onset of cirrhosis. At the end of the study, rats were sacrificed, livers were sectioned and stained to analyze disease progression and tumor nodules were counted. Liver function tests were performed to determine liver injury and overall liver function. Finally, genome-wide gene expression profiling on the surrounding, non-tumoral liver tissue was used to monitor the “field effect” in response to EGCG. Results: EGCG significantly (p < 0.01) prevented the development of HCC tumor nodules from on average 18.8 in vehicle controls to on average 9.1 in EGCG-treated animals. EGCG also reduced liver injury and improved liver function as assessed by serum chemistry tests. Finally, a gene expression signature predictive of poor survival and HCC development in human cirrhosis patients was reversed in response to EGCG. Conclusions: Our data are consistent with the growing body of evidence suggesting that EGCG has protective effects in liver disease. Further, our results suggest that EGCG is a potentially effective HCC prevention strategy that can be monitored using gene expression signatures.
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