Aspirin Affects Tumor Angiogenesis and Sensitizes Human Glioblastoma Endothelial Cells to Temozolomide, Bevacizumab, and Sunitinib, Impairing Vascular Endothelial Growth Factor-Related Signaling

World Neurosurgery
Stefania Elena NavoneGiovanni Marfia

Abstract

Glioblastoma (GBM) is the most common and fatal human brain tumor, with the worst prognosis. The aberrant microenvironment, enhanced by the activation of proangiogenic mediators such as hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and their downstream effectors, sustain GBM malignancy. Proangiogenic signaling represents an attractive chemotherapeutic target. Recent evidence suggests a therapeutic benefit from aspirin (acetylsalicylic acid, or ASA) intake in reducing risk and cancer progression. In the present study, human primary GBM-endothelial cells (ECs) were used to ascertain whether ASA could inhibit angiogenesis and improve cell sensitivity to drugs. The impact of ASA was observed by measuring cell viability, tube-like structure formation, migration, VEGF production, and proliferative, proangiogenic, and apoptotic modulators expression, such as HIF-1α/VEGF/vascular endothelial growth factor receptor/(VEGFR)-1/VEGFR-2, Ras/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinase/AKT signaling axis, and Bcl-2-associated X protein/B-cell lymphoma 2 (BCL-2) ratio. Furthermore, we evaluated the effect of ASA alone or in combination with temozol...Continue Reading

Citations

May 1, 2019·Journal of Cancer Research and Clinical Oncology·Xiao ZhangXiaobo Li
May 31, 2020·Glycobiology·Matías A PibuelSilvia E Hajos
Jul 28, 2020·Pharmaceuticals·Angel Escamilla-RamírezCristina Trejo-Solís
Nov 16, 2019·European Journal of Pharmacology·Michał AntoszczakAdam Huczyński
Nov 3, 2020·Current Tissue Microenvironment Reports·LaDeidra Monet Roberts, Jennifer Munson
Mar 4, 2021·European Journal of Pharmacology·Shiyuan XieBin Yang
Jun 3, 2021·Journal of Clinical Medicine·Dominika SiwikAleksandra Gąsecka

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