Elucidation of the mechanisms of α-linolenic acid and its derivative in the treatment of non-small cell lung cancer using network pharmacology

Purpose: α-Linolenic acid (ALA) and its derivative docosahexaenoic acid (DHA) have been reported to play an anticancer role in multiple types of cancer. However, their molecular targets in treating non-small cell lung cancer (NSCLC) have not been investigated. Methods The common target genes of NSCLC, ALA and DHA were obtained by intersections between disease and drug databases. The common targets were imported into the STRING database to build a PPI network. The hub genes were selected in Cytoscape. GO and KEGG analyses were performed to reveal the function of potential targets, and the prognosis of hub genes was obtained by KM analysis. Moreover, molecular docking of target molecules and ligands was carried out using AuToDock software to select the ligand‒receptor with the lowest binding energy for molecular dynamics simulation. Results A total of 8357 targets of NSCLC, 15 targets of ALA and DHA, 12 common targets of diseases and drugs, and 9 targets of PPI interactions were obtained. The Kaplan‒Meier plotter showed that the mRNA expression of the 3 hub genes was significantly associated with overall survival (OS) and first progression survival (FPS) in NSCLC patients. These results showed good binding between the drug components and the hub targets. Molecular docking and molecular dynamics simulations demonstrated that the binding of RXRA and DHA tends to be stable. Conclusions In this study, we investigated the basic pharmacological effects of ALA and DHA in treating NSCLC and concluded that ALA and DHA have multitarget and multipathway actions in the treatment of NSCLC.