Polygonatum sibiricum Polysaccharide Inhibited Liver Cancer in a Simulated Tumor Microenvironment by Eliminating...

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Liver cancer is a highly aggressive malignancy with limited treatment options.
• Traditional Chinese Medicine (TCM) shows potential in combating cancer proliferation and metastasis.
• Investigating novel therapeutic agents for liver cancer is crucial.

Purpose of the Study:

• To explore the anti-cancer effects of Polygonatum sibiricum polysaccharide (PSP) on liver cancer cells.
• To investigate PSP's impact on the tumor immune microenvironment.
• To elucidate the underlying molecular mechanisms of PSP's action.

Main Methods:

• HepG2 and Hep3B liver cancer cells were treated with varying concentrations of PSP.
• Dendritic cells (DCs) were co-cultured with cancer cell supernatant to simulate the tumor microenvironment.
• Cell proliferation, apoptosis, migration, invasion, epithelial-to-mesenchymal transition (EMT), and DC inflammatory responses were assessed.
• Key signaling pathways, including Toll-like receptor 4 (TLR4)/Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB), were analyzed.

Main Results:

• PSP significantly inhibited proliferation, migration, invasion, and EMT in liver cancer cells in a dose-dependent manner.
• PSP promoted apoptosis in HepG2 and Hep3B cells.
• PSP induced an inflammatory response in DCs, increasing levels of IL-6, IL-1β, and TNF-α.
• PSP suppressed the activation of TLR4/STAT3 and NF-κB signaling pathways.
• Lipopolysaccharide (LPS), a TLR4 agonist, reversed the anti-cancer effects of PSP.

Conclusions:

• PSP exhibits potent anti-cancer properties against liver cancer by affecting both cancer cells and the tumor immune microenvironment.
• PSP's mechanism involves the inhibition of the TLR4/STAT3 signaling pathway.
• PSP represents a promising alternative therapeutic agent for liver cancer treatment.