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Fluorene-9-bisphenol inhibits epithelial-mesenchymal transition of human endometrial cancer Ishikawa cells by repressing TGF-β signaling pathway

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Abstract

Fluorene-9-bisphenol (BHPF), a new derivative of bisphenol A (BPA), has been introduced for treatment with estrogen-related tumors, such as endometrial cancer. This study investigated the potential mechanism underlying the action of BHPF against endometrial cancer in vitro. We used the cell counting kit-8 (CCK8) method on Ishikawa cells to screen sub-lethal doses of BHPF and established the optimal concentration at which BHPF influenced the proliferation of Ishikawa cells. Effect of BHPF on cell migration and invasion was investigated by cell scratch assay and transwell assay, respectively. Expression levels of epithelial-mesenchymal transition (EMT)–related proteins were detected by Western blot analysis. BHPF was found to inhibit the proliferation of Ishikawa cells, whose migration and invasion abilities were also reduced. Western blot indicated that BHPF can significantly inhibit the EMT process of Ishikawa cells by blocking transforming growth factor-β (TGF-β) signaling pathway. This is the first report of the effect of BHPF on the biological behavior of endometrial cancer cells and its inhibition of endometrial cancer progression by repressing both endometrial cell proliferation and epithelial-mesenchymal transition, hence suggesting it as a novel anti-cancer drug.

Schematic representation of the molecular basis underlying BHPF treatment. BHPF repressed the EMT process by regulating EMT-related genes, such as E-cadherin, N-cadherin, and vimentin as well as the TGF-β signaling pathway–related genes, including p-Smad2/3 and slug, in a BHPF-dependent manner.

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Acknowledgments

We thank Dr. Zhaobin Zhang for his assistance with the preparation of BHPF samples.

Funding

This work was supported by the Beijing Municipal Science & Technology Commission for capital characteristic clinic project (Grant No. Z141107002514128).

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Authors and Affiliations

  1. Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100050, China

    Lingjuan Wang & Wei Wei

  2. Department of Pediatrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100050, China

    Taifeng Zhuang

  3. Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, 200127, China

    Fangzhou Li

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  1. Lingjuan Wang
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  2. Taifeng Zhuang
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  3. Fangzhou Li
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  4. Wei Wei
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Correspondence to Wei Wei.

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Responsible editor: Philippe Garrigues

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Wang, L., Zhuang, T., Li, F. et al. Fluorene-9-bisphenol inhibits epithelial-mesenchymal transition of human endometrial cancer Ishikawa cells by repressing TGF-β signaling pathway. Environ Sci Pollut Res 26, 27407–27413 (2019). https://doi.org/10.1007/s11356-019-05184-0

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