Multiomics and experimental validation reveal theophylline's mechanism targeting IL1A/ACTB/TLR4 and identify synergistic drugs in hepatocellular carcinoma - PubMed
3 hours ago
- #Theophylline
- #Multiomics
- #Hepatocellular carcinoma
- The study investigates theophylline's mechanism in hepatocellular carcinoma (HCC) through multiomics and experimental validation.
- Core targets identified: IL1A (interleukin 1α), ACTB (actin β), and TLR4 (toll-like receptor 4).
- Theophylline shows stable binding to core targets via molecular docking and dynamics simulations.
- Potential synergistic drugs identified: chlorogenic acid, losartan, and estrone sulfate.
- Core targets linked to clinical stage, prognosis, immune cell infiltration, and immune checkpoints in HCC.
- Single-cell and spatial transcriptomics reveal heterogeneous expression of core targets in the tumor microenvironment.
- Experimental validation confirms theophylline inhibits HCC cell proliferation, migration, and invasion in vitro and in vivo.
- Theophylline may influence the tumor immune microenvironment and gut microbiota-liver axis.
- Findings support repurposing theophylline as a therapeutic or adjuvant for HCC and suggest combination therapies.