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Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

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Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

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Acknowledgments

This work was supported by the National Natural Science Foundations of China (No. 81872335), the National Natural Science Youth Foundation (No. 81902486), the Natural Science Foundation of Henan (No. 161100510300), the Central Plains Science and Technology Innovation Leading Talents (No. 224200510015), the Science and Technology Project of Henan Province (No. 212102310187).

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. The Pathophysiology Department, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China

    Yubing Zhou, Xinyu He, Yanan Jiang, Zitong Wang, Yin Yu, Wenjie Wu, Chenyang Zhang, Jincheng Li, Yaping Guo, Xinhuan Chen, Jimin Zhao, Kangdong Liu & Zigang Dong

  2. The China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China

    Yubing Zhou, Xinyu He, Yanan Jiang, Yin Yu, Wenjie Wu, Kangdong Liu & Zigang Dong

  3. State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450000, China

    Yanan Jiang, Yaping Guo, Xinhuan Chen, Jimin Zhao, Kangdong Liu & Zigang Dong

  4. Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, 450000, China

    Yanan Jiang, Zhicai Liu, Jimin Zhao & Kangdong Liu

  5. Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, 450000, China

    Jimin Zhao, Kangdong Liu & Zigang Dong

  6. Oncology Department, The Tumor Hospital of Linzhou City, Linzhou, 456500, China

    Zhicai Liu

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  1. Yubing Zhou
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Corresponding authors

Correspondence to Kangdong Liu or Zigang Dong.

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Yubing Zhou, Xinyu He, Yanan Jiang, Zitong Wang, Yin Yu, Wenjie Wu, Chenyang Zhang, Jincheng Li, Yaping Guo, Xinhuan Chen, Zhicai Liu, Jimin Zhao, Kangdong Liu and Zigang Dong declare no competing interests. This study was approved by the Research Ethics Committee of Zhengzhou University. Written informed consent was provided by all patients for the use of the tissue samples.

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Zhou, Y., He, X., Jiang, Y. et al. Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma. Front. Med. 17, 290–303 (2023). https://doi.org/10.1007/s11684-022-0956-8

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  • DOI: https://doi.org/10.1007/s11684-022-0956-8

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