Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating β-catenin activation and EMT pathways
Pengxiang Min1
Yingying Li1
Cuirong Wang1
Junting Fan2
Shangming Liu1
Xiang Chen1
Yamin Tang3
Feng Han4
Aixia Zhang5
Lili Feng1
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,China2.Department of Pharmaceutical Analysis,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 210029,China3.Department of Analysis and Testing Center,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China4.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;Institute of Brain Science,the Affiliated Brain Hospital of Nanjing Medical University,Nanjing,Jiangsu 211166,China5.Department of Clinical Pharmacology,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 211166,China
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 of α-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelial-mesenchymal 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.
机标关键词：cateninpathwayscellsactivationcyclopeptideformedglioblastomainhibits
分类号：R739.41(神经系肿瘤)
论文发表日期：2024-07-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：13( 中插3,322-333 )
英文信息