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RSS FeedsIJMS, Vol. 21, Pages 1490: Glioblastoma Cells Do Not Affect Axitinib-Dependent Senescence of HUVECs in a Transwell Coculture Model (International Journal of Molecular Sciences)

 
 

21 february 2020 20:00:19

 
IJMS, Vol. 21, Pages 1490: Glioblastoma Cells Do Not Affect Axitinib-Dependent Senescence of HUVECs in a Transwell Coculture Model (International Journal of Molecular Sciences)
 


Axitinib is an orally available inhibitor of tyrosine kinases, with high specificity for vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. It is approved for the treatment of advanced renal cell carcinoma and is in phase II clinical trials for recurrent glioblastoma (GBM). GBM is a brain tumor peculiar in its ability to induce neoangiogenesis. Since both GBM tumor cells and endothelial cells of tumor vasculature express VEGFRs,Axitinib exerts its inhibitory action on both tumor and endothelial cells. We and others previously demonstrated that Axitinib triggers cellular senescence. In particular, Axitinib-dependent senescence of HUVECs (human umbilical vein endothelial cells) is accompanied by intracellular reactive oxygen species(ROS) increase and early ataxia telangiectasia mutated(ATM) activation. Here we wondered if the presence of glioblastoma tumor cells could affect the HUVEC senescence upon Axitinib exposure. To address this issue, we cocultured HUVECs together with GBM tumor cells in transwell plates. HUVEC senescence did not result in being affected by GBM cells, neither in terms of β galactosidase activity nor of proliferation index or ATM phosphorylation. Conversely, Axitinib modulation of HUVEC gene expression was altered by cocultured GBM cells. These data demonstrate that the GBM secretome modifies HUVECs’ transcriptomic profile upon Axitinib exposure, but does not prevent drug-induced senescence.


 
171 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 21, Pages 1491: GALNT14: An Emerging Marker Capable of Predicting Therapeutic Outcomes in Multiple Cancers (International Journal of Molecular Sciences)
IJMS, Vol. 21, Pages 1488: Small Molecule Anion Carriers Correct Abnormal Airway Surface Liquid Properties in Cystic Fibrosis Airway Epithelia (International Journal of Molecular Sciences)
 
 
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