The Effect of Citrus aurantium on Non-Small-Cell Lung Cancer: A Research Based on Network and Experimental Pharmacology

• Published in: BioMed research international 2023, Vol.2023 (1), p.6407588-6407588
• Main Authors: Yao, Liangliang, Zhang, Xuan, Huang, Chaoming, Cai, Yi, Wan, Chunpeng (Craig)
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antibodies; Arteriosclerosis; Atherosclerosis; Bioavailability; Bitter orange; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Care and treatment; Cell cycle; Cell proliferation; Chemical properties; Chinese medicine; Citrus; Citrus aurantium; Computer programs; Drugs, Chinese Herbal - pharmacology; ESR1 protein; Fruits; Gelatinase B; Genes; Health aspects; Herbal medicine; Identification and classification; Ingredients; Kinases; Lipids; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Matrix Metalloproteinase 9; Medical prognosis; Medicine, Chinese Traditional; Molecular Docking Simulation; mRNA; Non-small cell lung carcinoma; p53 Protein; Peroxisome Proliferator-Activated Receptors; Pharmacology; Physiological aspects; Phytochemicals; Proteins; Signal transduction; Signaling; Software; Statistical analysis; Traditional Chinese medicine; Variance analysis; Western blotting
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2023/6407588

Purpose. To screen the main active components of Citrus aurantium through a network pharmacology approach, construct a component-disease target network, explore its molecular mechanism for the treatment of non-small-cell lung cancer (NSCLC), and validate it experimentally. Methods. The active ingredients in Citrus aurantium and the targets of Citrus aurantium and NSCLC were collected through the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP), GeneCards, and OMIM databases. The protein interaction network was constructed using the STRING database, and the component-disease relationship network graph was analyzed using Cytoscape 3.9.1. The Metascape database can be used for GO and KEGG enrichment analyses. The Kaplan-Meier plotter was applied for overall survival analysis of key targets of Citrus aurantium in the treatment of NSCLC. Real-time PCR (RT-PCR) and Western blotting were used to determine the mRNA and protein levels of key targets of Citrus aurantium for the treatment of NSCLC. Results. Five active ingredients of Citrus aurantium were screened, and 54 potential targets for the treatment of NSCLC were found, of which the key ingredient was nobiletin and the key targets are TP53, CXCL8, ESR1, PPAR-α, and MMP9. GO and KEGG enrichment analyses indicated that the mechanism of nobiletin in treating NSCLC may be related to the regulation of cancer signaling pathway, phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, lipid and atherosclerosis signaling pathway, and neurodegenerative signaling pathway. The experimental results showed that nobiletin could inhibit the proliferation of NSCLC cells and upregulate the levels of P53 and PPAR-α and suppress the expression of MMP9 (P