Highlights
- •F16 treatment inhibits U87MG cell survival, migration, and invasion.
- •F16 exhibits potent anti-angiogenic and anti-tumor activities by selectively antagonizing Vascular Endothelial Growth Factor Receptor (VEGFR).
- •F16 is efficacious in delaying tumor growth in the subcutaneous xenograft model.
Abstract
Glioblastoma Multiforme (GBM) is one of the most aggressive and lethal types of all
cancers, with an average 5-year survival rate of 5%. Since GBM tumors are highly vascularized
tumors, and their growth is angiogenesis-dependent, antagonizing tumor angiogenesis
by using angiogenesis inhibitors were considered as one of the promising approaches.
In this context, intensive preclinical evaluation of a novel small molecule named
F16 has exhibited potent anti-angiogenic and anti-tumor activities by selectively
antagonizing Vascular Endothelial Growth Factor Receptor (VEGFR). Also, recent pharmacokinetic
evaluation of F16 with tissue distribution analysis has shown that this molecule is
transported across the blood-brain barrier (BBB) and accumulates in the brain regions
with no signs of neurotoxicity. Therefore, further studies were conducted to determine
the efficacy of F16 in delaying glioblastoma progression via inhibiting tumor angiogenesis. Our in vitro studies have clearly demonstrated the ability of F16 to inhibit migration and invasion
of U87MG cells and also confirmed a potent cytotoxic effect against these cells in
comparison to Temozolomide (TMZ). Our in vivo studies with the subcutaneously implanted (s.c.) xenograft tumor model and in vitro studies have clearly demonstrated the ability of F16 to delay tumor growth and inhibit
migration and invasion.
Graphical abstract
Graphical Abstract
Keywords
Abbreviations:
GBM (Glioblastoma Multiforme), TMZ (Temozolomide), BVZ (Bevacizumab), TBDE (Trypan Blue Dye Exclusion), VEGF (Vascular Endothelial Growth Factor), VEGFR (Vascular Endothelial Growth Factor Receptor), MMPs (Matrix Metalloproteinases)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: April 24, 2022
Accepted:
April 19,
2022
Received in revised form:
April 12,
2022
Received:
February 16,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
