Inhibition of Wnt/β-catenin increases anti-tumor activity by synergizing with sorafenib in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) poses a major global health challenge owing to limited treatment efficacy and drug resistance to therapies such as the tyrosine kinase inhibitor (TKI) sorafenib. We utilized a microfluidic three-dimensional (3D) drug testing system to assess drug responses in 37 fresh clinical samples and performed immunohistochemical analysis of 41 tumor tissue samples that received sorafenib therapy. Results revealed that Wnt/β-catenin activation was associated with sorafenib resistance, with higher nuclear β-catenin levels predicting poor response. Targeting Wnt/β-catenin via genetic intervention enhanced TKI sensitivity by promoting apoptosis and reducing clonogenicity. Through a large scale of drug and inhibitor library screening, we identified PRI-724, a potent CREB-bin

SUBMITTER: He Y 

PROVIDER: S-EPMC12216529 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature