A Systematic Study of Traditional Chinese Medicine for the Treatment of Lung Adenocarcinoma Using a Reverse Network of Key Targets Based on Bioinformatics and Molecular Docking: Curcumin and Trans-Resveratrol as Potential Drug Candidates for Lung Adenocarcinoma
Authors: Wang Wujun , Zeng Zhu , Zhang Junli , Sun Zengtao 
Published: May 2023

Background Lung adenocarcinoma (LUAD) is a dominant tumor with high morbidity and mortality. In spite of innovations in surgery, chemotherapy, and targeted therapies, the prognosis for patients with LUAD remains unsatisfactory. Therefore, it is particularly important to study the biological markers of the occurrence, development, and prognosis of this disease. Methods In this study, 3 datasets were selected from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using Database Annotation, Visualization and Integrated Discovery (DAVID). In addition, a protein-protein interaction network was performed and 10 key genes were analyzed. Gene and protein expression were analyzed using The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) databases, respectively. Then, overall survival (OS) rate was analyzed using Kaplan-Meier plotter database. The chemical components were downloaded from the HERB database. Finally, the chemical constituents were docked with 10 targets by molecular docking. By using in vitro studies, we evaluated the effects of curcumin and trans-resveratrol on the proliferation of LUAD cells. Results A total of 122 upregulated and 434 downregulated genes were identified. Then, 10 key genes (glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-1 beta (IL1B), von Willebrand factor (VWF), matrix metalloproteinase-9 (MMP9), CD44 antigen (CD44), transcription factor Jun (JUN), platelet endothelial cell adhesion molecule (PECAM1), hematopoietic progenitor cell antigen CD34 (CD34), peroxisome proliferator-activated receptor gamma (PPARG), and collagen alpha-1(I) chain (COL1A1)) were obtained. TCGA results showed that GAPDH, MMP9, and COL1A1 were upregulated, while IL-1B, VWF, CD44, JUN, PECAM1, CD34, and PPARG were downregulated in cancer tissues. Kaplan-Meier plotter analysis also showed that high expression of GAPDH, PPARG, and COL1A1, and low expression of VWF, PECAM1, CD34, PPARG, and COL1A1 were associated with poor prognosis in LUAD. Combined with gene expression, staging, immunohistochemistry, and OS prognostic analysis, the results showed that COL1A1 was a potential target for the occurrence and prognosis of LUAD. In addition, 2 key components (curcumin and trans-resveratrol) had good docking effect with COL1A1. We found that curcumin and trans-resveratrol significantly inhibited the proliferation of LUAD cells and significantly decreased the expression of COL1A1 and MMP9. Conclusion In conclusion, our study identified the potential target of LUAD and the main traditional Chinese medicine components (curcumin and trans-resveratrol) for LUAD treatment. This study provides potential therapeutic targets and treatment strategies for the treatment of LUAD.