Abstract
BACKGROUND: Kanglaite injection (KLTi) has shown good clinical efficacy in the treatment of pancreatic ductal adenocarcinoma (PDAC). While previous studies have demonstrated the antitumor effects of the oil compounds in KLTi, it is unclear whether the unsaponifiable matter (USM) also has antitumor effects. This study used network pharmacology, molecular docking, and database verification methods to investigate the molecular biological mechanisms of USM. METHODS: Compounds of USM were obtained from GC-MS, and targets from DrugBank. Next, the GEO database was searched for differentially expressed genes in cancerous tissues and healthy tissues of PDAC to identify targets. Subsequently, the protein-protein interaction of USM and PDAC targets was constructed by BisoGenet to extract candidate genes. The candidate genes were enriched using GO and KEGG by Metascape, and the gene-pathway network was constructed to screen the key genes. Molecular docking and molecular dynamic simulations of core compound targets were finally performed and to explore the diagnostic, survival, and prognosis value of targets. RESULTS: A total of 10 active compounds and 36 drug targets were screened for USM, 919 genes associated with PDAC, and 139 USM candidate genes against PDAC were excavated. The enrichment predicted USM by acting on RELA, NFKB1, IKBKG, JUN, MAPK1, TP53, and AKT1. Molecular docking and dynamic simulations confirmed the screened core targets had good affinity and stability with the corresponding compounds. In diagnostic ROC validation, the above targets have certain accuracy for diagnosing PDAC, and the combined diagnosis is more advantageous. As the most diagnostic value of RELA, it is equally significant in predicting disease-specific survival and progression-free interval. CONCLUSIONS: USM in KLTi plays an anti-PDAC role by intervening in the cell cycle, inducing apoptosis, and downregulating the NF-κB, MAPK, and PI3K-Akt pathways. It might participate in the pancreatic cancer pathway, and core target groups have diagnostic, survival, and prognosis value biomarker significance.