Exploration of Potential Targets and Mechanisms of Fisetin in the Treatment of Non-Small-Cell Lung Carcinoma via Network Pharmacology and In Vitro Validation

Purpose: The morbidity and fatality rates of non-small-cell lung cancer (NSCLC) were high, although a combination of multiple treatments was used. Fisetin, a small flavonoid compound, had shown anticancer activities. Thus, we aimed at exploring the mechanisms of Fisetin in the treatment of NSCLC. Methods: TCMSP and Swiss target tools were used to screen the targets of Fisetin, and GeneCards was used to collect the genes related to NSCLC. The genes common to Fisetin and NSCLC were obtained by Venn analysis, whose possible functions were further annotated. A "Compound-Target-Disease" network was then constructed and hub genes were filtered. Also, molecular docking was performed to predict the binding abilities between Fisetin and the hub genes. Then, the effects of Fisetin on the expression of hub genes in lung adenocarcinoma cells were preliminarily evaluated in vitro. Results: A total of 131 genes common to Fisetin and NSCLC were filtered out, which might be enriched in several biological processes including antioxidation, cell proliferation, and various signaling pathways, such as PI3K-Akt and IL-17 signaling pathways. Among them, PIK3R1, CTNNB1, JUN, EGFR, and APP might be the hub genes. Molecular docking indicated the close bond between Fisetin and them. Experiments implied a possible effect of Fisetin on the expression of hub genes in A549 cells. Conclusion: The present study found a series of novel targets and pathways for Fisetin treating NSCLC. Multiple angles, targets, and pathways were involved in the biological processes, which need to be verified in further experiments.