Exploring the mechanism of action of Platycodon grandiflorum in the treatment of NSCLC by combining molecular docking and network pharmacology

Objective: Non-small cell lung cancer (NSCLC), as the most common type of lung cancer, has a high rate of metastasis and mortality. A large number of studies have proved that traditional Chinese medicine has the effect of anti-drug resistance and targeting of cancer cells. Platycodon platycodon can treat lung cancer, but its potential drug targets and molecular mechanisms in the treatment of NSCLC have not been fully clarified. Methods: The key components, potential core targets and main pathways of Platycodon grandiflorum were obtained by constructing the drug ingredient-disease-target network. Finally, the interaction between the selected compounds and proteins was docking and evaluated by means of molecular docking. GEPIA, HPA and Kaplan-Meier databases were used to analyze the expression of differential genes and core proteins of the core targets in tumor tissue and normal lung tissue and their survival analysis. Results: A total of 7 active ingredients and 240 component target genes were screened. Molecular docking results showed that the screened compounds had stable binding force with core targets. Differential gene analysis showed that mRNA expressions of key genes AKT1, TNF and ESR1 were up-regulated in lung cancer tissues compared with normal lung tissues. The mRNA expression of TP53 was down-regulated, and the mRNA expression of EGFR was not significantly changed. Survival analysis showed that the expression of five key genes, AKT1, TP53, TNF, EGFR and ESR1, were significantly correlated with poor prognosis (Log-rank p < 0.05). Conclusion: Platycodon grandiflorum in the treatment of NSCLC mainly involves acacetin, luteolin, Spinasterol and other key components. These compounds appear to exert their therapeutic effects by modulating the AGE-RAGE pathway, subsequently affecting proteins such as AKT1, TP53, TNF, EGFR, and ESR1, thereby contributing to the treatment of NSCLC. EGFR gene and Spinasterol compound should be considered in this study.