Picroside Ⅱ Inhibits Glycolysis and Migration in HepG2 Cells

Abstract

Objectives: The objective of this study was to investigate the impacts and mechanisms of Picroside II on hepatocellular carcinoma (HCC). Materials and Methods: The GeneCards database was mined for HCC-related targets. The targets of Picroside Ⅱ were predicted using PharmMapper and SwissTarget Prediction. The molecular complex detection (MCODE) plugin in Cytoscape was used to screen core genes. The DAVID database was subsequently used to enrich the core targets by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), which was used to determine the possible mode of action of Picroside II on HCC. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) examined core targets and patient mortality. Auto Dock 4.2.6 was used to simulate the docking of potential targets with Picroside II. Then, surface plasmon resonance (SPR) was used to validate the targets’ docking ability. Finally, Western blotting and in vitro experiments were used to evaluate the effect of Picroside II on HepG2 cells. Results: The result of network pharmacology showed that 94 genes may be possible targets for Picroside II treating of HCC, with GPI, LGALS3, SRC, HRAS, HSP90AA1, MMP9, PPARG, SERPINE1, and VEGFA being the most promising. GPI and Picroside II have strong virtual docking capabilities, and SPR tests verified their binding ability. In vitro studies revealed that Picroside II could suppress HepG2 cell migration. It has been demonstrated that Picroside II can stop tumors from migrating by attaching to the glycolytic proteins GPI and suppressing the downstream glycolytic pathway proteins ALDOA and GAPDH. Picroside II’s potential new target for treating tumors is GPI. Conclusion: The results of this study suggest that Picroside Ⅱ can affect glucose metabolism by binding to glycolytic protein GPI and that this protein is a potential new target for Picroside Ⅱ in the treatment of tumors.