Network Pharmacology-based Elucidation of Molecular Biological Mechanisms of Kanglaite Injection for Treatment of Pancreatic Ductal Adenocarcinoma [post]

Jie Lj, Bowen Xu, Wenchao Dan, Xiaoxiao Zhang, Luchang Cao, Shixin Li
2020 unpublished
Background: Kanglaite injection (KLTi) has shown good clinical efficacy in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, its molecular biological mechanisms are still unclear. This study used network pharmacology approach to investigate the molecular biological mechanisms of KLTi.Methods: Compounds in KLTi were screened using TCMSP and drug targets were obtained from the DRUGBANK. Next, the GEO database was searched for differentially expressed genes in cancerous tissues
more » ... healthy tissues of PDAC patients to identify targets. Subsequently, the protein-protein interaction data of KLTi and PDAC targets were constructed by BisoGenet. A visual analysis was done to extract KLTi candidate genes for PDAC. The candidate genes were enriched using GO and KEGG by Metascape, and the gene-pathway network was constructed to further screen the key genes.Results: A total of 10 active compounds and 36 drug targets were screened for KLTi, 919 differentially expressed genes associated with PDAC were identified from GEO, and 139 KLTi candidate genes against PDAC were excavated by BisoGenet. The gene-pathway network showed RELA, NFKB1, IKBKG, JUN, MAPK1, TP53, and AKT1 as the core genes, predicting that KLTi intervenes in PDAC by acting on these genes.Conclusions: Our study suggested that KLTi plays an anti-PDAC role by intervening in the cell cycle, inducing apoptosis, regulating protein binding, inhibiting nerve invasion, and down-regulating the NF-κB, MAPK, and PI3K-Akt signaling pathways. In addition, it might also directly participate in the pancreatic cancer pathway. These results provide new evidence and therapeutic direction for subsequent clinical applications and basic research on KLTi in PDAC.
doi:10.21203/rs.3.rs-19866/v1 fatcat:tftki74vgjgipdoo3xtdzlhqze