Regorafenib and Nifuroxazide exert enhanced suppression of hepatocellular carcinoma by inhibiting STAT3 and immune remodeling.

Regorafenib, a multi‑kinase inhibitor, has limited efficacy in hepatocellular carcinoma (HCC) due to dose‑-dependent toxicity. The present study explored whether low‑dose Regorafenib combined with Nifuroxazide exerts enhanced anti‑tumor effects in HCC models. In vitro experiments with HepG2 cells showed the combination inhibited cell viability, proliferation and migration, induced apoptosis and reduced expression of key proteins, including phosphorylated signal transducer and activator of transcription 3 (STAT3). In vivo, H22 tumor‑bearing mice treated with the combination exhibited suppressed tumor growth without systemic toxicity, along with changes in apoptotic proteins, enhanced tumor‑infiltrating immune cells and improved systemic immune responses. These findings indicated that the combination exerts enhanced suppression of HCC by inhibiting STAT3 and remodeling anti‑tumor immunity, providing preclinical evidence for a safe and effective strategy.