Exploring targets and related mechanisms of Scutellaria baicalensis for treating non-small cell lung cancer based on network pharmacology

Background Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers, the leading cause of cancer-related deaths worldwide. Despite recent advancements in NSCLC treatment, such as targeted therapy and immunotherapy, a large proportion of NSCLC patients develop drug resistance. Thus, development of new effective treatments for NSCLC is urgently needed. Traditional Chinese medicine may provide sources for developing new anti-cancer drugs. Although Scutellaria baicalensis (SB) has been proven to have anti-cancer effects, its action mechanism on NSCLC is not yet fully understood. Here we used network pharmacology to investigate the potential mechanism of SB treating NSCLC. Methods We identified the active constituents of SB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and predicted their potential targets using the SwissTargetPrediction database. Next, therapeutic targets for NSCLC were screened using five databases: GeneCards, DisGeNET, DrugBank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). A protein-protein interaction (PPI) network of the common targets between SB and NSCLC was constructed using STRING were visualized using Cytoscape. We also performed enrichment analysis of these targets to identify gene ontology (GO) and KEGG pathways associated with them. Finally, we conducted molecular docking analysis using Autodock Vina and PyMOL to investigate the interactions between active SB components and NSCLC targets. Furthermore, we performed in vitro experimental validations of the findings by bioinformatics analysis. Results We identified 35 active compounds of SB and their 463 potential targets, and 1,073 NSCLC-associated targets. A total of 140 targets overlapped between the SB and NSCLC targets. PPI network analysis and drug-ingredient-target network analysis identified SRC, HSP90AA1, STAT3, AKT1, and MAPK3 as the core target proteins, and baicalein, 5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone, skullcapflavone II, tenaxin I, and rivularin as critical active compounds of SB. GO and pathway enrichment analysis uncovered pathways significantly associated with the common targets between SB and NSCLC, including PI3K-Akt signaling, VEGF, and EGFR tyrosine kinase inhibitor resistance. Molecular docking revealed a stable binding between the main active components and core targets. In vitro experiments showed that baicalein suppressed A549 cell proliferation in a concentration-dependent manner, induced apoptosis, and caused cell cycle arrest in the S phase. Moreover, baicalein inhibited A549 cell migration and activation of the PI3K/Akt pathway. Conclusions SB has a potential to treat NSCLC through multiple targets and pathways. This study afforded potential targets for further experimental research to explore the mechanism of SB in the treatment of NSCLC.