2. Academic Validation
  3. Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer

Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer

  • Mol Med. 2024 Sep 28;30(1):166. doi: 10.1186/s10020-024-00928-2.
Zhixuan Wu # 1 2,  Haoyi Xiang # 3 4,  Xiaowu Wang # 5,  Rongrong Zhang # 2,  Yangyang Guo 2,  Liangchen Qu 6,  Jingyao Zhou 7,  Yanyi Xiao 8 9
Affiliations

Affiliations

  • 1 The Dingli Clinical College of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
  • 2 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, China.
  • 3 Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310016, China.
  • 4 Department of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang Province, 310016, China.
  • 5 Department of Burns and Skin Repair Surgery, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, 325200, China.
  • 6 Emergency Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 318000, China. 1106083035@qq.com.
  • 7 Pharmacy Department, Taizhou Central Hospital, Taizhou, Zhejiang Province, 318000, China. 15057619295@139.com.
  • 8 The Dingli Clinical College of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China. 15967411128@163.com.
  • 9 Department of Thyroid and Breast Surgery, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang Province, 325000, China. 15967411128@163.com.
  • # Contributed equally.
PMID: 39342122 DOI: 10.1186/s10020-024-00928-2
Abstract

Background: Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast Cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action.

Methods: We employed weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the GeneCards database to identify potential targets for TNBC. Simultaneously, we utilized the Swiss Target Prediction, ChEMBL, and STITCH databases to identify potential targets of nomilin. The core targets and mechanisms of nomilin against TNBC were predicted through protein-protein interaction (PPI) network analysis, molecular docking, and enrichment analysis. The results of the network pharmacology were corroborated by conducting experiments.

Results: A total of 17,204 TNBC targets were screened, and 301 potential targets of nomilin were identified. Through the PPI network, eight core targets of nomilin against TNBC were pinpointed, namely BCL2, Caspase3, CyclinD1, EGFR, HSP90AA1, KRAS, PARP1, and TNF. Molecular docking, molecular dynamics simulation and proteome microarray revealed that nomilin exhibits strong binding activity to these core proteins. Enrichment analysis results indicated that the anti-TNBC effect of nomilin is associated with PI3K/Akt pathway. In vitro and in vivo experiments have demonstrated that nomilin inhibits TNBC cell proliferation and migration while promoting cell Apoptosis through the PI3K/Akt pathway.

Conclusion: For the first time, the research effectively discovered the objectives and mechanisms of nomilin in combating TNBC using network pharmacology, molecular docking, molecular dynamics simulation, proteome microarray and experimental confirmation, presenting a hopeful approach for treating TNBC.

Keywords

Molecular docking; Network pharmacology; Nomilin; PI3K/Akt pathway; Triple negative breast cancer.

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