Silica Nanoparticle-modified Bupleurum Inhibits the Secretion of Extracellular Vesicles of Liver Cancer Cells and the Progression of Liver Cancer Through p38 Mitogen-activated Protein Kinase (MAPK)/Interleukin-6 Pathway

Background: Bupleurum is an active ingredient extracted from the Chinese medicine bupleurum, which has been proven to have various biological effects, such as anti-tumor, anti-inflammatory, and immune regulation. However, its application is limited by factors such as low bioavailability and poor stability. In addition, extracellular vesicle secretion by liver cancer cells is involved in the formation and progression of liver cancer. The p38 mitogen-activated protein kinase (MAPK) and interleukin (IL)-6 pathways are two signaling pathways related to the development of liver cancer. Objectives: By modifying SiNPs and bupleurum, we tried to inhibit these two signaling pathways to achieve a therapeutic effect on liver cancer. Materials and Methods: HepG2 cells were cultured and used in group experiments to explore how bupleurum regulates the p38 MAPK/IL-6 pathway and exerts inhibition by using SB202190, p38 MAPK agonists, and inhibitors and agonists of IL-6 in liver cancer. Results: SiNPs-SS has a stronger inhibitory effect on liver cancer than SS and inhibits the secretion of extracellular vesicles and progression of liver cancer by inhibiting the p38 MAPK/IL-6 pathway. Conclusion: SiNPs-SS inhibits the secretion of extracellular vesicles and the progression of liver cancer by inhibiting the p38 MAPK/IL-6 pathway.