Astragaloside IV promotes apoptosis of pancreatic cancer cells by activating endoplasmic reticulum stress through PERK/ATF4/CHOP signaling pathways

Objectives: Pancreatic cancer ranks as the 12th most common malignant tumor worldwide, characterized by short survival periods and poor treatment outcomes. Astragaloside IV (AST-IV), the primary pharmacological component of Astragalus membranaceus, represents a traditional Chinese medicinal with demonstrated anticancer potential. This study investigates the therapeutic efficacy of AST-IV against pancreatic cancer while elucidating its underlying mechanisms of action, thereby providing novel insights and theoretical foundations for both the clinical application of AST-IV and the treatment of pancreatic cancer.Methods: In this study, we initially assessed the effects of AST-IV on pancreatic cancer cells through cell viability assays. Subsequently, we employed RNA-seq analysis to investigate the underlying mechanisms of AST-IV action. Finally, we conducted further validation studies to elucidate the potential molecular mechanisms of AST-IV.Results: Our findings demonstrate that AST-IV effectively suppresses the proliferation and migration capabilities of pancreatic cancer cells. To elucidate the underlying mechanisms, RNA-seq analysis revealed that AST-IV potently induces endoplasmic reticulum (ER) stress, modulates intracellular Ca concentrations, and influences critical cellular processes including cell cycle regulation and DNA damage repair. Further mechanistic investigations demonstrated that AST-IV significantly activates the PERK signaling pathway, leading to upregulation of ATF4 expression. This cascade subsequently induces marked overexpression of CHOP, ultimately triggering apoptotic.Conclusion: In summary, our findings demonstrate that AST-IV induces pancreatic cancer cell apoptosis through PERK-mediated endoplasmic reticulum stress. These results not only expand the potential therapeutic applications of AST-IV, but also provide novel theoretical foundations for developing innovative treatment strategies and identifying therapeutic targets for pancreatic cancer.