Network Pharmacology Revealed the mechanism of Platycodon grandiflorum in Lung Cancer Treatment

Abstract

Background: Traditional Chinese Medicine has demonstrated increasingly unique advantages in the treatment of lung cancer. Through literature review, it was found out that Platycodon grandiflorum had immunomodulatory and anti-inflammatory effects, and it had a special targeting effect on the lung. Purpose：In order to determine the molecular mechanism of Platycodon grandiflorum in lung cancer treatment. Network pharmacology theory was used to do a systematic study.Methods: The active compounds of Platycodon grandiflorum were screened from TCMSP database. Then, compounds targets were predicted with the assistance of Swiss Target Prediction and STITCH. The targets of lung cancer were screened form TTD and DisGeNET database. The common targets of compounds and lung cancer were screened out for following analysis. A Protein-Protein Interaction (PPI) Network was constructed by STRING. Subsequent to topological analysis, the hub targets were screened out for KEGG pathway and GO Enrichment. Molecular docking by AutoVina was performed to investigate the binding ability between the hub targets and compounds. Results: There were 4 active compounds screened out, including Acacetin, Spinasterol, cis-Dihydroquercetin and Luteolin. There were 80 targets screened as the common target of compounds and lung cancer. After topological analysis TP53, AKT1, VEGFA, CASP3, IL6, EGFR and MAPK1 were identified as hub targets. The 7 hub targets might be involved in 81 biological annotation and in the regulation of 23 pathways to intervene lung cancer. The main functional annotation was negative regulation of apoptotic process. Almost all of the pathways were directly or indirectly associated with the PI3K-Akt signal pathway and MAPK signal pathway. According to Affinity score of molecular docking the best binding protein for Luteolin was EGFR, and the best binding protein for Acacetin was CASP3. This meant that the Platycodon grandiflorum was easier to combine these two targets than other targets.Conclusion: Our study affirmed the effectiveness of Platycodon grandiflorum in treatment of lung cancer from molecular level. And we found that EGFR and CASP3 were the most likely targets for the direct action of Platycodon grandiflorum. The most important pathways that Platycodon grandiflori might interfere with were PI3K-Akt signaling pathway and MAPK signaling pathway.