Soluble Flt-1 Has Cytotoxic Effects on BeWo Choriocarcinoma Cells.
Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis and is overexpressed in many kinds of malignant tumors. Soluble VEGF receptor 1 (sVEGFR-1/ soluble fms-like tyrosine kinase 1 [sFlt-1]) plays a role as an inhibitor of VEGF, and an antitumor effect has been shown in several studies using sFlt-1. Recently, in addition to its antiangiogenic effect, it was reported that sFlt-1 has direct cytotoxicity.



Transfection of sFlt-1 plasmid DNA was performed in the BeWo choriocarcinoma cell line. Overexpression of sFlt-1 in BeWo cells was confirmed by ELISA. In order to evaluate cell proliferation, cell counting and BrdU uptake assay were performed. Cytotoxicity was tested by LDH assay. TdT-Mediated dUTP Nick end Labeling (TUNEL) staining and quantitative analysis of caspase-cleaved keratin 18 (ccK18) level were done to evaluate cell apoptosis.



The cell number was significantly less, and the ratio of cytotoxicity was significantly higher in sFlt-1 group compared to the control group. TUNEL staining and ccK18 level suggested nonapoptotic cell death.



Soluble Flt-1 showed a cytotoxic effect on BeWo cells. Our results suggest that sFLT-1 could be therapeutic for malignant tumors.
1 Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, Japan.
Michiko
M
Yamashita
1 Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, Japan.
Keiichi
K
Kumasawa
1 Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, Japan.
Tatsuya
T
Miyake
1 Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, Japan.
Hitomi
H
Nakamura
1 Department of Obstetrics and Gynecology, Osaka University Hospital, Osaka, Japan.
Tadashi
T
Kimura
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002822:Choriocarcinoma / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008565:Membrane Proteins; C098069:PIGF protein, human; D042461:Vascular Endothelial Growth Factor A; D007770:L-Lactate Dehydrogenase; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
choriocarcinoma; cytotoxicity; sVEGFR-1/sFLT-1