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

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 (AAT). However, there are still a lack of the effective drugs that target VM formation in GBM. In the present study, we evaluate the effects of a plant cyclopeptide moroidin on VM formed by GBM cells and explore its underlying molecular mechanisms. Moroidin evidently suppressed migration, tube formation and expression of α-SMA and metalloproteinase-9 in human GBM cell lines at sub-lethal concentrations. RNA sequencing data suggested the involvement of EMT pathway in the mechanism of moroidin. Exposing GBM cells to moroidin, the expression of EMT marker N-Cadherin and Vimentin decreased in a concentration-dependent manner. Moreover, moroidin significantly reduced the level of phosphorylated ERK and inhibited the activation β-catenin. The plant cyclopeptide moroidin inhibited the VM formed by GBM cells by inhibiting ERK/β-catenin-mediated EMT. Our study indicates a promising application of moroidin as an anti-VM agent to the treatment of GBM.