Details

Autor(en) / Beteiligte

• Wan, Weifeng
• Zhang, Xin
• Huang, Changren
• Chen, Ligang
• Yang, Xiaobo
• Bao, Kunyang
• Peng, Tangming

Titel

Monensin inhibits glioblastoma angiogenesis via targeting multiple growth factor receptor signaling

Ist Teil von

• Biochemical and biophysical research communications, 2020-09, Vol.530 (2), p.479-484

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Glioblastoma is characterized by the extensive vascularization with poor prognosis. Targeting both tumor cell and angiogenesis may present an effective therapeutic strategy for glioblastoma. Monensin, a polyether ionophore antibiotic, has been recently recognized as promising anticancer drug candidate due to its potent and selective anti-tumor activities. However, little is known on the effects of monensin on tumor angiogenesis. In this work, we investigated the effects and underlying mechanisms of monensin on glioblastoma angiogenesis and growth. We show that monensin at nanomolar concentrations inhibits early stages of capillary network formation of glioblastoma endothelial cell. Monensin inhibited multiple endothelial cellular events, including migration, growth and survival, without affecting adhesion to Matrigel. We further demonstrate that monensin acts on endothelial cells via suppressing VEGFR- and EGFR-mediated signaling pathways. Monensin also inhibits proliferation and induces apoptosis in a panel of glioblastoma cells. However, monensin is more effective in targeting endothelial cells than tumor cells. Using glioblastoma growth xenograft mice model, we show that monensin at tolerable dose effectively inhibits glioblastoma growth. Of note, there is a significant decreased tumor vascularization from monensin-treated mice. Our work clearly demonstrates the anti-angiogenic activity of monensin and its ability in suppressing multiple tyrosine kinase receptor-mediated pathways. Our findings suggest that is a useful addition to the treatment armamentarium for glioblastoma. •Monensin at nanomolar concentration inhibits glioblastoma angiogenesis.•Monensin at micromolar concentration inhibits glioblastoma cells.•Monensin inhibits glioblastoma angiogenesis and growth in mice.•Monensin inhibits multiple tyrosine kinase receptor-mediated signaling pathways.