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Verteporfin Exerts Anticancer Effects and Reverses Resistance to Paclitaxel via Inducing Ferroptosis in Esophageal Squamous Cell Cancer Cells

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Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Ferroptosis is a new form of regulated cell death and targeting ferroptosis provides a novel therapeutic approach for human cancers. Verteporfin (VP) has been identified as a Yes-associated protein (YAP) inhibitor for treatment of several human cancers. However, it remains unclear whether VP exerts anticancer activity by inducing ferroptosis in ESCC cells. In the current study, we found that VP reduced cell viability and led to cell death in ESCC cell lines (KYSE150 and KYSE30) by inhibiting YAP expression. Subsequently, the findings revealed that VP treatment triggered significant ferroptosis events, including accumulation of Fe2+, reactive oxygen species (ROS) and malondialdehyde (MDA), reduction of mitochondrial membrane potential (MMP), glutathione (GSH) and glutathione peroxidase 4 (GPX4) expression. Further study showed that the effects of ESCC cell proliferation and death caused by VP could be reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Moreover, VP enhanced the chemosensitivity of ESCC resistant cells to paclitaxel (PTX). And VP combined with PTX can synergistically inhibit cell proliferation and induce cell death by triggering ferroptosis of PTX-resistant cells. All these data suggested that VP suppressed ESCC cell survival and reversed resistance to PTX through inducing ferroptosis, which may provide a promising therapeutic strategy for ESCC.

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All data generated or analyzed during this study are included in this published article.

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Funding

This research was supported by the National Natural Science Foundation of China (No. 82272911), the Natural Science Foundation of Shanxi Province, China (No. 202103021224385), Research Project Supported by Shanxi Scholarship Council of China (2023-098).

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Author notes

  1. Xue-Wei Wang and Zi-Yi Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, 030001, China

    Xue-Wei Wang, Zi-Yi Yang, Ting Li, Xin-Ran Zhao & Xiao-Xia Wang

  2. Department of Infectious Diseases, Shanxi Provincial People’s Hospital, Affiliated People’s Hospital of Shanxi Medical University, Taiyuan, 030012, China

    Xiao-Zhong Li

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  1. Xue-Wei Wang
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Contributions

Conceptualization, methodology, investigation were done by XWW and ZYY; methodology was done by TL and XRZ; conceptualization, resources, supervision, writing—review and editing were done by XZL and XXW.

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Correspondence to Xiao-Zhong Li or Xiao-Xia Wang.

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Wang, XW., Yang, ZY., Li, T. et al. Verteporfin Exerts Anticancer Effects and Reverses Resistance to Paclitaxel via Inducing Ferroptosis in Esophageal Squamous Cell Cancer Cells. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00891-z

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