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Soluble Flt-1 Has Cytotoxic Effects on BeWo Choriocarcinoma Cells

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Osaka University Hospital, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan

    Michiko Yamashita MD, Keiichi Kumasawa MD, PhD, Tatsuya Miyake MD, PhD, Hitomi Nakamura PhD & Tadashi Kimura MD, PhD

Authors
  1. Michiko Yamashita MD
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  2. Keiichi Kumasawa MD, PhD
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  3. Tatsuya Miyake MD, PhD
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  4. Hitomi Nakamura PhD
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  5. Tadashi Kimura MD, PhD
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Correspondence to Keiichi Kumasawa MD, PhD.

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Yamashita, M., Kumasawa, K., Miyake, T. et al. Soluble Flt-1 Has Cytotoxic Effects on BeWo Choriocarcinoma Cells. Reprod. Sci. 25, 830–836 (2018). https://doi.org/10.1177/1933719117698575

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