Abstract
Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1/sFLT1) is an angiogenesis inhibitor that competes with angiogenic factors such as VEGF and Placental Growth Factor (PlGF). Imbalances of VEGF and sFLT1 levels can cause pathological conditions such as tumour growth or preeclampsia. We observed direct damage caused by sFLT1 in tumour cells. We exposed several kinds of cells derived from ovarian and colorectal cancers as well as HEK293T cells to sFLT1 in two ways, transfection and exogenous application. The cell morphology and an LDH assay revealed cytotoxicity. Additional experiments were performed to clarify how sFLT1 injured cells. In this study, non-apoptotic cell damage was found to be induced by sFLT1. Moreover, sFLT1 showed an anti-tumour effect in a mouse model of ovarian cancer. Our results suggest that sFLT1 has potential as a cancer therapeutic candidate.
Highlights
In a previous study[1,2,3,4], we developed a mouse model of preeclampsia by overexpressing placenta-specific human sFLT1
We confirmed that sFLT1 induced cytotoxicity by measuring growth inhibition, lactate dehydrogenase (LDH) release and necrotic cellular morphology
Caspase-3 expression and transferase-mediated dUTP nick-end labelling (TUNEL) staining in sFLT1-expressing cells indicated that the cellular damage was not caused by apoptosis
Summary
In a previous study[1,2,3,4], we developed a mouse model of preeclampsia by overexpressing placenta-specific human sFLT1 (hsFLT1). In these mice, only transduction of sFLT1 decreased placental weight. Several studies have demonstrated proliferative suppression by sFLT1 which caused apoptosis in an endothelial cell line[11] and suppressed vascular development in the labyrinthine layer in a preeclampsia mouse model[4]. We investigated the anti-tumour effect of exogenous rVEGFR1, endogenous sFLT1, and bevacizumab using mice transplanted with SKOV3 cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
