首页|Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway
Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway
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The spreading of cancer cells from the primary tumor site to other parts of the body,known as metastasis,is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer(TNBC).Overexpression of epidermal growth factor receptor(EGFR)is observed in approximately 70％of TNBC patients.EGFR is crucial for promoting tumor metastasis and associated with poor prognosis.Therefore,it is vital to identify effective therapeutic strategies targeting EGFR inhibition.Ononin,an isoflavonoid found in various plants,such as clover and soybeans,has been shown to have anticancer properties in several cancers.In the present study,we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular pathways.We used various assays,including cell viability,colony formation,Transwell,wound healing,ELISA,Western blotting,and staining techniques,to achieve this objective.The results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis,as evidenced by the cell viability assay,colony formation assay,and expression of apoptosis markers,and reduced the metastatic capabilities of TNBC cells.These effects were achieved through the direct suppression of cell adhesion,invasiveness and motility.Furthermore,in TNBC xenograft lung metastatic models,ononin treatment significantly reduced tumor growth and lung metastasis.Additionally,ononin reversed the epithelial-mesenchymal transition(EMT)by downregulating the expression of EMT markers and matrix metalloproteinases,as confirmed by Western blot analysis.Further-more,ononin treatment reduced EGFR phosphorylation and suppressed the PI3K,Akt,and mTOR signaling pathways,which was further confirmed using EGFR agonists or inhibitors.Importantly,ononin treatment did not exert any toxic effects on liver or kidney function.In conclusion,our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFR-mediated PI3K/Akt/mTOR pathway.Further studies are warranted to validate its efficacy and explore its potential clinical applications.
ononinTNBCbreast cancer lung metastasisEGFRPI3k/AktEMTtherapeutic effect
School of Chinese Medicine,LKS Faculty of Medicine,The University of Hong Kong,Hong Kong 999077,China
School of Pharmacy,Southwest Medical University,Education Ministry Key Laboratory of Medical Electrophysiology,Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation,Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica,Southwest Medical University,Luzhou 646000,China
College of Food Science,South China Agricultural University,Guangzhou 510642,China
State Key Laboratory of Oncology in South China,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510080,China
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Guangxi Science and Technology Key Research and Development Program
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