胶质母细胞瘤（GBM）是一种高度血管化的恶性脑肿瘤，临床结果不佳。由侵袭性 GBM 细胞形成的血管生成拟态 (VM) 是肿瘤血液供应的另一种方法，并导致抗血管生成治疗 (AAT) 的失败。然而，目前仍缺乏针对GBM VM形成的有效药物。在本研究中，我们评估了植物环肽moroidin对GBM细胞形成VM的影响，并探讨其潜在的分子机制。 Moroidin 在亚致死浓度下明显抑制人 GBM 细胞系中的迁移、管形成以及 α-SMA 和金属蛋白酶-9 的表达。 RNA测序数据表明EMT途径参与了moroidin的作用机制。将GBM细胞暴露于moroidin后，EMT标志物N-Cadherin和Vimentin的表达以浓度依赖性方式下降。此外，moroidin 显着降低磷酸化 ERK 的水平并抑制 β-catenin 的活化。植物环肽moroidin通过抑制ERK/β-catenin介导的EMT来抑制GBM细胞形成VM。我们的研究表明，桑蚕苷作为抗 VM 药物在 GBM 治疗中具有广阔的应用前景。

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.