The First Affiliated Hospital, Department of Medical Oncology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
The First Affiliated Hospital, Department of General Practice, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Mol Divers. 2023 Jun;27(3):1437-1457. doi: 10.1007/s11030-022-10501-w. Epub 2022 Aug 6.
Non-small cell lung cancer (NSCLC) is one of the leading causes of death in the world. Rhubarb, a traditional Chinese medicine, has been widely used in the treatment of inflammatory and autoimmune diseases. This study aimed to investigate the possible mechanism of the rhubarb herb in the treatment of NSCLC by means of network pharmacology and molecular docking and to provide a theoretical basis for experiments and clinical application of traditional Chinese medicine for treating lung cancer. The main active chemical components and targets of rhubarb were screened through Swiss Target Prediction, TargetNet, and Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The protein-protein interaction (PPI) network was built via an in-depth exploration of the relationships between the proteins. The enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to predict the potential roles in the pathogenesis of NSCLC via the R package cluster Profiler. Potential targets and active ingredients associated with anti-tumor effects of rhubarb were screened by reverse molecular docking. By searching databases and literature, a total of 295 targets were found for the 21 active ingredients in rhubarb. There were 68 common target genes associated with NSCLC, of which 9 are derived from FDA-approved drugs. GO Gene Set Enrichment Analysis (GSEA) explored up to 1103 biological processes, 62 molecular functions, and 18 cellular components. KEGG GSEA explored 65 basic pathways, and 71 disease pathways. Four key targets (JUN, EGFR, BCL2, and JAK2) were screened through the protein-protein interaction network, target-pathway network, and FDA drug-target network. Molecular docking results showed that these key targets had relatively strong binding activities with rhubarb's active ingredients. The present study explored the potential pharmacological mechanisms of rhubarb on NSCLC, promoting the clinical application of rhubarb in treating NSCLC, and providing references for advanced research.
非小细胞肺癌（NSCLC）是全球主要致死病因之一。大黄作为一种传统中药，在治疗炎症和自身免疫性疾病方面得到了广泛应用。本研究旨在采用网络药理学和分子对接方法，探讨大黄治疗 NSCLC 的可能作用机制，为中药治疗肺癌的实验和临床应用提供理论依据。通过瑞士靶标预测（Swiss Target Prediction）、TargetNet 和中药系统药理学数据库（TCMSP）筛选大黄的主要活性化学物质和靶点，通过深入挖掘蛋白之间的关系构建蛋白-蛋白相互作用（PPI）网络，运用 R 包 cluster Profiler 对基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行富集分析，预测大黄治疗 NSCLC 发病机制中的潜在作用。通过反向分子对接筛选与大黄抗肿瘤作用相关的潜在靶点和活性成分。通过数据库和文献检索，共找到大黄 21 种活性成分的 295 个作用靶点，其中有 68 个与 NSCLC 相关的共同靶点，其中 9 个来自 FDA 批准的药物。GO 基因集富集分析（GSEA）探索了多达 1103 个生物学过程、62 个分子功能和 18 个细胞成分，KEGG GSEA 探索了 65 个基础通路和 71 个疾病通路。通过蛋白质-蛋白质相互作用网络、靶点-通路网络和 FDA 药物-靶点网络筛选出 4 个关键靶点（JUN、EGFR、BCL2 和 JAK2）。分子对接结果表明，这些关键靶点与大黄的活性成分具有较强的结合活性。本研究探讨了大黄治疗 NSCLC 的潜在药理学机制，促进了大黄在治疗 NSCLC 中的临床应用，为深入研究提供了参考。
