Senescence‑associated IL‑33 secretion undermines sorafenib efficacy in hepatocellular carcinoma via immune evasion.

ABSTRACT: Hepatocellular carcinoma (HCC) is a highly lethal cancer with increasing incidence rates worldwide. The recommended treatments for advanced‑stage HCC are sorafenib and regorafenib; however, developing resistance to these medications significantly limits their effectiveness, and the underlying mechanisms are poorly understood. The present study demonstrated that interleukin‑33 (IL‑33) promotes sorafenib resistance via immune regulation. In vitro, western blotting and reverse transcription‑quantitative PCR showed that both sorafenib and regorafenib treatments led to an increase in the upregulation and secretion of IL‑33 through a positive feedback loop involving the IL‑33/transmembrane suppression of tumorigenicity 2 (ST2L) pathway. Senescence‑associated β‑galactosidase staining and w

SUBMITTER: Lin YX 

PROVIDER: S-EPMC12456110 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature