Vascular endothelial growth factor receptor 2 (VEGFR2) correlates with long-term survival in patients with advanced high-grade serous ovarian cancer (HGSOC): a study from the Tumor Bank Ovarian Cancer (TOC) Consortium

2019 ◽  
Vol 145 (4) ◽  
pp. 1063-1073 ◽  
Author(s):  
Jun Guan ◽  
Silvia Darb-Esfahani ◽  
Rolf Richter ◽  
Eliane T. Taube ◽  
Ilary Ruscito ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Term Survival ◽  
Endothelial Growth Factor

scholarly journals Transient Exposure of Endothelial Cells to Doxorubicin Leads to Long-Lasting Vascular Endothelial Growth Factor Receptor 2 Downregulation

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 210
Author(s):  
Silvia Graziani ◽  
Luca Scorrano ◽  
Giovanna Pontarin
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Drug Withdrawal ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
P53 Expression ◽  
Endothelial Growth Factor

Doxorubicin (Dox) is an effective antineoplastic drug with serious cardiotoxic side effects that persist after drug withdrawal and can lead to heart failure. Dysregulation of vascular endothelium has been linked to the development of Dox-induced cardiotoxicity, but it is unclear whether and how transient exposure to Dox leads to long-term downregulation of Endothelial Vascular Endothelial Growth Factor Receptor type2 (VEGFR2), essential for endothelial cells function. Using an in vitro model devised to study the long-lasting effects of brief endothelial cells exposure to Dox, we show that Dox leads to sustained protein synthesis inhibition and VEGFR2 downregulation. Transient Dox treatment led to the development of long-term senescence associated with a reduction in VEGFR2 levels that persisted days after drug withdrawal. By analyzing VEGFR2 turnover, we ruled out that its downregulation was depended on Dox-induced autophagy. Conversely, Dox induced p53 expression, reduced mTOR-dependent translation, and inhibited global protein synthesis. Our data contribute to a mechanistic basis to the permanent damage caused to endothelial cells by short-term Dox treatment.

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