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

Pancreatic cancer is characterized by short survival and poor treatment outcomes. Astragaloside IV (AST‑IV), the primary pharmacological component of Astragalus membranaceus, is a traditional Chinese medicinal component with demonstrated anticancer potential. The present study aimed to evaluate the therapeutic efficacy of AST‑IV against pancreatic cancer cells in vitro and to elucidate its underlying mechanisms of action, thereby providing novel insights for its clinical application in the treatment of pancreatic cancer. The effects of AST‑IV on PANC‑1 pancreatic cancer cell viability and migration were assessed using Cell Counting Kit‑8 and wound healing assays, respectively. Subsequently, RNA‑sequencing (RNA‑seq) analysis was performed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to investigate the mechanisms underlying the effects of AST‑IV. Finally, western blotting experiments were conducted to validate the potential molecular mechanisms of AST‑IV. The results revealed that AST‑IV effectively suppressed the proliferation and migration of the pancreatic cancer cells. In addition, GO and KEGG analyses of the differentially expressed genes identified by RNA‑seq analysis suggested that AST‑IV induced endoplasmic reticulum (ER) stress and influenced critical cellular processes, including cell cycle regulation and DNA damage repair. Furthermore, western blotting demonstrated that AST‑IV significantly activated the protein kinase R‑like endoplasmic reticulum kinase (PERK) signaling pathway, upregulated activating transcription factor 4 expression and induced the overexpression of CCAAT/enhancer‑binding protein homologous protein, indicating that it triggered apoptosis. In summary, these findings suggest that AST‑IV induced apoptosis in pancreatic cancer cells through PERK‑mediated ER stress. These results expand the potential therapeutic applications of AST‑IV and provide a theoretical foundation for the development of novel treatment strategies and therapeutic targets for pancreatic cancer treatment.