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Metformin Induces Human Esophageal Carcinoma Cell Pyroptosis by Targeting the miR-497/PELP1 Axis
Cancer Letters
  • Lu Wang
  • Kai Li
  • Xianjie Lin
  • Zhimeng Yao
  • Shuhong Wang
  • Xiao Xiong
  • Zhifeng Ning
  • Jing Wang
  • Xiaozheng Xu
  • Yi Jiang
  • Ditian Liu
  • Yuping Chen
  • Dianzheng Zhang, Philadelphia College of Osteopathic Medicine
  • Hao Zhang
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Evasion of apoptosis is a major contributing factor to the development of chemo- and radiotherapy resistance. Therefore, activation of non-apoptotic programmed cell death (PCD) could be an effective alternative against apoptosis-resistant cancers. In this study, we demonstrated in vitro and in vivo that metformin can induce pyroptosis, a non-apoptotic PCD, in esophageal squamous cell carcinoma (ESCC), a commonly known chemo-refractory cancer, especially at its advanced stages. Proline-, glutamic acid- and leucine-rich protein-1 (PELP1) is a scaffolding oncogene and upregulated PELP1 in advanced stages of ESCC is highly associated with cancer progression and patient outcomes. Intriguingly, metformin treatment leads to gasdermin D (GSDMD)-mediated pyroptosis, which is abrogated by forced expression of PELP1. Mechanistically, metformin induces pyroptosis of ESCC by targeting miR-497/PELP1 axis. Our findings suggest that metformin and any other pyroptosis-inducing reagents could serve as alternative treatments for chemo- and radiotherapy refractory ESCC or other cancers sharing the same pyroptosis mechanisms.

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This article was published in Cancer Letters, Volume 450, pages 22-31.

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Copyright © 2019 Elsevier B.V.

Citation Information
Lu Wang, Kai Li, Xianjie Lin, Zhimeng Yao, et al.. "Metformin Induces Human Esophageal Carcinoma Cell Pyroptosis by Targeting the miR-497/PELP1 Axis" Cancer Letters Vol. 450 (2019) p. 22 - 31
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