BMS-1 synergistically promotes the anti-tumor effect of regorafenib on hepatocellular carcinoma

Background Regorafenib is an oral multitarget tyrosine kinase inhibitor that plays a critical anti-tumor role. However, regorafenib resistance affects the prognosis of hepatocellular carcinoma (HCC) patients. This study explored the combined use of regorafenib and the small-molecule programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor, BMS-1 to provide new therapeutic strategies for HCC. Methods To determine the underlying anti-tumor mechanism of regorafenib in combination with BMS-1, we performed several assays, including cell proliferation and apoptosis assays, in three hepatoma cell lines and verified the results in vivo in nude mice. Results The combination of regorafenib and BMS-1 significantly inhibited the proliferation, invasion, and migration of hepatoma cells and promoted their apoptosis, compared to monotherapy. Using molecular docking, BMS-1 was predicted to bind directly to the PD-L1 dimer. In an immune environment containing peripheral blood mononuclear cells, PD-L1 expression was significantly reduced when the two-drug combination was administered. Additionally, regorafenib combined with BMS-1 markedly inhibited the growth of HCC xenograft tumors in vivo. Conclusions The combination of regorafenib and BMS-1 improved the anti-HCC efficacy of regorafenib both in vitro and in vivo. The synergistic anti-tumor effect may involve PD-L1 regulation, suggesting that combining immunotherapy with targeted drugs could provide a novel treatment option for HCC patients.