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ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway

Science China(Life Sciences) 2024年第9期67卷 1849-1866页

作者： Kumar Ganesan Cong Xu Jianming Wu Bing Du Qingqing Liu Yue Sui Cailu Song Jinhui Zhang Hailin Tang Jianping Chen School of Chinese Medicine LKS Faculty of MedicineThe University of Hong KongHong Kong 999077China School of Pharmacy Southwest Medical UniversityEducation Ministry Key Laboratory of Medical ElectrophysiologySichuan Key Medical Laboratory of New Drug Discovery and Druggability EvaluationLuzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaSouthwest Medical UniversityLuzhou 646000China College of Food Science South China Agricultural UniversityGuangzhou 510642China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510080China

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 *** is crucial for promoting tumor metastasis and associated with poor ***,it is vital to identify effective therapeutic strategies targeting EGFR ***,an isoflavonoid found in various plants,such as clover and soybeans,has been shown to have anticancer properties in several *** the present study,we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular *** used various assays,including cell viability,colony formation,Transwell,wound healing,ELISA,Western blotting,and staining techniques,to achieve this *** 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 *** effects were achieved through the direct suppression of cell adhesion,invasiveness and ***,in TNBC xenograft lung metastatic models,ononin treatment significantly reduced tumor growth and lung ***,ononin reversed the epithelial-mesenchymal transition(EMT)by downregulating the expression of EMT markers and matrix metalloproteinases,as confirmed by Western blot ***,ononin treatment reduced EGFR phosphorylation and suppressed the PI3K,Akt,and m TOR signaling pathways,which was further confirmed using EGFR agonists or ***,ononin treatment did not exert any toxic effects on liver or kidney *** conclusion,our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFRm

关键词： ononin TNBC breast cancer lung metastasis EGFR PI3k/Akt EMT therapeutic effect

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