Soluble VEGF receptor 1 (sFLT1) induces non-apoptotic death in ovarian and colorectal cancer cells.
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.
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Tatsuya
T
Miyake
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Keiichi
K
Kumasawa
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Noriko
N
Sato
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Tsuyoshi
T
Takiuchi
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Hitomi
H
Nakamura
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Tadashi
T
Kimura
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D003603:Cytotoxins / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D000970:Antineoplastic Agents; D003603:Cytotoxins; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1