Centipede Polypeptide Affects the Inflammatory Reaction and Ferroptosis of Liver Cancer Cells Through the p53/TRAIL Pathway.

Various extracts from centipedes have therapeutic effects on liver cancer. This study aims to illustrate the impact and mechanism of centipede polypeptide (CP) on liver cancer. The suitable CP concentration and liver cancer cells were screened through CCK-8 analysis. The expression of proteins was analysed by Western blot. The level of cytokines and markers was measured by ELISA and biochemical kits. The apoptosis rate of cells was analysed by TUNEL staining and flow cytometry. Histopathological changes were observed by HE staining. The expression of Ki-67 and caspase-3 was assessed by IHC staining. The combination of CP and p53 was simulated by molecular docking. 200 μg/mL CP and HepG2 cells were applied in experiments. CP significantly upregulated p53, TNF-associated apoptosis-inducing ligand (TRAIL), TRADD and TRAF expression in HepG2 cells and tumour tissues (p < 0.05), suggesting p53-dependent activation of the TRAIL pathway. CP raised the levels of IL-6, IL-1β, TNF-α, MDA and ROS, and decreased those of IL-10, TGF-β1 and SOD in HepG2 cell supernatant and serum of nude mice (p < 0.05). CP promoted cell apoptosis and reduced the levels of ALT and AST to inhibit the progression of cancer. Molecular docking showed that CP could bind stably to p53 (p < 0.05). Silencing of p53 restrained the activation of the p53/TRAIL pathway and reduced the level of inflammatory reaction and ferroptosis, thus reversing the therapeutic effect of CP on liver cancer (p < 0.05). CP affected the inflammatory reaction and ferroptosis of liver cancer cells through the p53/TRAIL pathway.