Aim
To explore the potential mechanism of the treatment of lung cancer (LC) with Codonopsis Radix.-Hedysarum Multijugum Maxim.-Atractylodes Macrocephala Koidz. (CHA).
Conclusion
For LC, CHA exerts tumor-suppressive effects through various bioactive components, acting on multiple targets and signaling pathways.
Methods
The active ingredients and targets of CHA were obtained from TCMSP and SwissTargetPrediction databases. LC-related genes were obtained from MalaCards, GeneCards and DisGenNET databases. A protein-protein interaction network was constructed using STRING database, and analyzed with Cystoscape software. The core targets of CHA in LC treatment were determined by topological analysis, and functional annotation of these targets was performed via Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The binding ability of the target to the active ingredient was evaluated by molecular docking. CCK-8 assay, Transwell assay, qRT-PCR, Western blot and lung metastasis model in nude mice were used to evaluate the effects of CHA on the viability, migration and invasion of LC cells.
Results
27 active components and 411 common targets of CHA in lung cancer treatment were obtained. The common targets were associated multiple biological processes and pathways including PI3K-AKT pathway. 12-senecioyl-2E,8E,10E-atractylentriol, 14-acetyl-12-senecioyl-2E,8Z,10E-atractylentriol, astrapterocarpan, isoflavanone, (R)-Isomucronulatol were identified as the main bioactive components of CHA, and SRC, HSP90AA1, AKT1, EGFR, ESR1 were identified as core targets of CHA in LC treatment. The bioactive ingredients had good binding ability with the core targets. CHA significantly inhibited the viability, migration and invasion of LC cells, and also suppressed the transcription of core genes, and repressed the activation of PI3K/AKT pathway.