Abstract
Background: In recent years, the incidence and mortality rates of non-small cell lung cancer (NSCLC) have increased significantly. Shan Ci Gu is commonly used as an anticancer drug in traditional Chinese medicine; however, its specific mechanism against NSCLC has not yet been elucidated. Here, the mechanism was clarified through network pharmacology and molecular docking. Methods: The Traditional Chinese Medicine Systems Pharmacology database was searched for the active ingredients of Shan Ci Gu, and the relevant targets in the Swiss Target Prediction database were obtained according to the structure of the active ingredients. GeneCards were searched for NSCLC-related disease targets. We obtained the cross-target using VENNY to obtain the core targets. The core targets were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins database, and Cytoscape software was used to operate a mesh chart. R software was used to analyze the Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The core targets and active compounds were molecularly docked through Auto-Dock Vina software to predict the detailed molecular mechanism of Shan Ci Gu for NSCLC treatment. We did a simple survival analysis with hub gene to assess the prognosis of NSCLC patients. Results: Three compounds were screened to obtain 143 target genes and 1,226 targets related to NSCLC, of which 56 genes were related to NSCLC treatment. Shan Ci Gu treatment for NSCLC involved many BPs and acted on main targets including epidermal growth factor receptor (EGFR), ESR1, and SRC through signaling pathways including the endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathways. Shan Ci Gu might be beneficial for treating NSCLC by inhibiting cell proliferation and migration. Molecular docking revealed that the active compounds β-sitosterol, stigmasterol, and 2-methoxy-9,10-dihydrophenanthrene-4,5-diol had good affinity with the core target genes (EGFR, SRC, and ESR1). Core targets included EGFR, SRC, ESR1, ERBB2, MTOR, MCL1, matrix metalloproteinase 2 (MMP2), MMP9, KDR, and JAK2. Key KEGG pathways included endocrine resistance, EGFR tyrosine kinase inhibitor resistance, ErbB signaling, PI3K-Akt signaling, and Rap1 signaling pathways. These core targets and pathways have an inhibitory effect on the proliferation of NSCLC cells. Conclusion: Shan Ci Gu can treat NSCLC through a multi-target, multi-pathway molecular mechanism and effectively improve NSCLC prognosis. This study could serve as a reference for further mechanistic research on wider application of Shan Ci Gu for NSCLC treatment.
Highlights
Lung cancer is a malignant tumor with the highest incidence and mortality rates in China (Zhu et al, 2020), with cough, hemoptysis, chest pain, fever, and shortness of breath being the main clinical manifestations
By using network pharmacology and molecular docking, we aimed to explore the mechanism of action of Shan Ci Gu for the treatment of Non-small cell lung cancer (NSCLC) to improve the condition of patients with NSCLC and reduce mortality rates
The names of the compounds collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database were entered into the PubChem database and the SMILE and 3D “Standard Delay Format” (SDF) structures of the corresponding compounds were downloaded for the prediction of target genes and molecular docking
Summary
Lung cancer is a malignant tumor with the highest incidence and mortality rates in China (Zhu et al, 2020), with cough, hemoptysis, chest pain, fever, and shortness of breath being the main clinical manifestations. Over the past 50 years, the incidence and mortality rates of lung cancer have increased significantly in many countries, and it ranks first among the causes of death from malignant tumors in China’s urban citizens. NSCLC treatment has achieved certain efficacy through the use of targeted therapy, but all of the commonly used drugs have a single pathway and are subject to increasing drug resistance. The use of Chinese medicine in combination with the commonly used drugs and treatments can enhance the effectiveness of conventional treatment, reduce drug resistance, reduce adverse effects and toxicity, alleviate patient suffering, and improve the quality of life (Su et al, 2020). The incidence and mortality rates of non-small cell lung cancer (NSCLC) have increased significantly. The mechanism was clarified through network pharmacology and molecular docking
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