Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes

Abstract

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.