ArticleInternational journal of biological sciences2026
Combining sorafenib with spermine and sphingosine synergistically enhances anticancer efficacy by modulating metabolic pathways and gut microbiome in hepatocellular carcinoma.
Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Deciphering Lipid Metabolic Landscape of Sorafenib-Treated Hepatocellular Carcinoma by Mass Spectrometry Imaging and Transcriptomics.Biomolecules · 2026Article
- Identification of a Novel PDRG1-EZH2-p21 Pathway Controlling Senescence and Tumor Progression in Hepatocellular Carcinoma.International journal of biological sciences · 2026Article
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Authors and funding
9 authors.
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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 triggered cell cycle arrest at the S phase, while sphingosine and sorafenib induced G1 arrest, contributing to an increased sub-G1 population and apoptosis when combined. Notably, sorafenib treatment led to the downregulation of
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