Astragalus Polysaccharide Regulates Epithelial-mesenchymal Transition in HepG2 Liver Cancer Cells by Inhibiting NLRP3 Inflammasome Activation

Background Epithelial-mesenchymal transition (EMT) is crucial in liver cancer progression. Developing novel medicines to disrupt the progression of EMT might be a novel approach in managing liver cancer. Purpose This study investigates the protective role of Astragalus polysaccharide (APS), a bioactive compound derived from Astragalus membranaceus, in modulating EMT in HepG2 liver cancer cells. Methods The effects of APS on EMT progression were evaluated by assessing cell viability, proliferation, invasion, migration, cell cycle, and apoptosis in HepG2 cells. Furthermore, the involvement of the NOD-like receptor protein 3 (NLRP3) inflammasome in this process was explored. Results Results: APS treatment significantly inhibited the viability, proliferation, invasion, and migration of HepG2 cells while promoting cell cycle arrest and apoptosis. Notably, APS reduced the expression of NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein, and caspase-1, while decreasing the levels of inflammatory cytokines. In addition, the activator Nigericin dampened the effect of APS by partially rescuing the activity of NLRP3. Specifically, Nigericin promoted the development of EMT inhibited by APS and exacerbated the malignant transformation of HepG2 cells improved by APS. Conclusion Our findings demonstrated the function of APS in liver cancer and the process by which APS inhibits NLRP3 inflammasome activation to protect the EMT of HepG2 cells. Our results showed that by targeting NLRP3, the application of APS appears to be a viable tactic for preventing the progression of liver cancer.