A novel strategy for sorafenib-resistant hepatocellular carcinoma: autotaxin Inhibition by PF-8380.

ABSTRACT: By inhibiting the conversion of lysophosphatidylcholine into lysophosphatidic acid, a process pivotal to tumor progression, the autotaxin (ATX) inhibitor PF-8380 offers a new anticancer therapeutic strategy, distinct from the action mechanism of sorafenib. This study explored the potential anticancer effects of the PF-8380 on hepatocellular carcinoma (HCC) cells, especially sorafenib-resistant strains. The investigation included both in vitro and in vivo experiments to evaluate the impact of PF-8380 treatment on epithelial-mesenchymal transition (EMT) and autophagy markers. An orthotopic HCC model served as the in vivo platform. PF-8380 showed a significant reduction in cell viability in both sorafenib-susceptible and resistant HCC cells. It effectively altered EMT by increasing E-cadherin

SUBMITTER: Kwak BJ 

PROVIDER: S-EPMC11906571 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature