Soluble Flt-1 Has Cytotoxic Effects on BeWo Choriocarcinoma Cells. (June 2018)

• Record Type: Journal Article
• Authors: Yamashita, Michiko; Kumasawa, Keiichi; Miyake, Tatsuya; Nakamura, Hitomi; Kimura, Tadashi
• Is Part Of: Reproductive sciences. Volume 25:Number 6(2018:Jun.)
• Page Start: 830
• Page End: 836
• Publication Date: 2018-06
• Subjects: sVEGFR-1/sFLT-1 -- cytotoxicity -- choriocarcinoma; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719117698575
• Languages: English
• ISSNs: 1933-7191

Abstract

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: Soluble Flt-1 showed a cytotoxic effect on BeWo cells. Our results suggest that sFLT-1 could be therapeutic for malignant tumors.