Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Aidi Injection Treating of Nonsmall Cell Lung Cancer

Aidi injection (ADI) is a compound preparation injection of Chinese herbs used to treat patients of nonsmall cell lung cancer (NSCLC) in China. This study aimed to reveal the mechanism of ADI in the treatment of NSCLC by using network pharmacology and molecular docking.

The related targets of ADI and NSCLC were obtained from multiple databases. The network diagram of disease-drug-components-targets (DDCT) and protein-protein interaction (PPI) was constructed to screen key targets. Then, the key targets and main signaling pathways were screened by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Next, in order to validate the results of network pharmacology, expression analysis and survival analysis of key genes were performed. Finally, we carried out the technology of molecular docking to further validate the accuracy of the above results.

A total of 207 targets of ADI and 5282 targets of NSCLC were obtained finally. Through the construction of DDCT and PPI network diagrams, 28 key targets were finally obtained. The results of the KEGG enrichment analysis indicated that multiple signaling pathways were associated with NSCLC, which included the MAPK signaling pathway, the IL-17 signaling pathway, and the PI3K/AKT signaling pathway. The key genes in the signaling pathway mainly include TP53, CASP3, MMP9, AKT1, PTGS2, and MAPK1. The results of differently expressed analysis of key genes showed that TP53, CASP3, MMP9, AKT1, PTGS2, and MAPK1 had statistical differences in lung squamous cell carcinoma (LUSC) compared with normal tissue (p < 0.001). In lung adenocarcinoma (LUAD), the expression of TP53, CASP3, MMP9, AKT1, and PTGS2 had statistical differences compared with normal tissue (p < 0.001), while the expression of MAPK1 had no statistical difference (p > 0.05). The results of survival analysis of key genes showed that AKT1, MAPK1, CASP3, MMP9, TP53, and PTGS2 had statistical differences in the OS or RFS of NSCLC patients (p < 0.05). In addition, the results of molecular docking indicated that the key genes and the main components have good docking activity.

This study revealed the potential mechanism of ADI in the treatment of NSCLC with multipathways and multitargets and provided a scientific basis for the in-depth study of ADI in the treatment of NSCLC.