Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating β-catenin activation and EMT pathways  

作　　者：Pengxiang Min Yingying Li Cuirong Wang Junting Fan Shangming Liu Xiang Chen Yamin Tang Feng Han Aixia Zhang Lili Feng 

机构地区：[1]Key Laboratory of Cardiovascular&Cerebrovascular Medicine,International Joint Laboratory for Drug Target of Critical Illnesses,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 211166,China [2]Department of Pharmaceutical Analysis,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 210029,China [3]Department of Analysis and Testing Center,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China [4]Institute of Brain Science,the Affiliated Brain Hospital of Nanjing Medical University,Nanjing,Jiangsu 211166,China [5]Department of Clinical Pharmacology,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 211166,China

出　　处：《Journal of Biomedical Research》2024年第4期322-333,共12页生物医学研究杂志（英文版）

基　　金：This work was supported by the National Key Research and Development Program of China(Grant No.2022YFE0104800 to Feng Han);the National Natural Science Foundation of China(Grant No.82003764 to Lili Feng);the Project supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.19KJB350001 to Lili Feng).

摘　　要：Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy.To date,there is still a lack of effective drugs that target VM formation in GBM.In the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular mechanisms.Moroidin significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of moroidin.Exposure to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM cells.Moreover,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-catenin.Finally,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated EMT.Therefore,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM.

关 键 词：moroidin vasculogenic mimicry GLIOBLASTOMA EMT Β-CATENIN 

分 类 号：R739.41[医药卫生—肿瘤]