Combining sorafenib with spermine and sphingosine synergistically enhances anticancer efficacy by modulating metabolic pathways and gut microbiome in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC), which makes up about 90% of liver cancer, is the third leading cause of cancer-related death. Recent studies suggest that metabolites derived from the gut microbiome may offer new therapeutic opportunities for HCC. In this study, we explored whether microbial metabolites could enhance the effectiveness of sorafenib, a first-line multi-kinase inhibitor used in advanced HCC. Through a screen of a microbiome metabolite library, we identified spermine and sphingosine as potential candidates that boosted anticancer effects of sorafenib in HepG2, Huh7, and SK-Hep-1 cells. These metabolites worked synergistically with sorafenib to suppress tumor growth in cultured HCC cells, patients-derived HCC organoids, and a xenograft mouse model. Mechanistically, spermine trig

SUBMITTER: Jang HR 

PROVIDER: S-EPMC12836515 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature