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Metformin induces human esophageal carcinoma cell pyroptosis by targeting the miR-497/PELP1 axis

Lu Wang1, Kai Li1, Xianjie Lin2

  • 1Department of Gastrointestinal Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China; Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, China; Cancer Research Centre, Shantou University Medical College, Shantou, Guangdong, China.

Cancer Letters
|February 17, 2019
PubMed

Insights

Metformin induces pyroptosis, a programmed cell death, in esophageal squamous cell carcinoma (ESCC) that resists chemotherapy. This discovery offers new treatment avenues for refractory cancers by targeting the miR-497/PELP1 axis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Apoptosis evasion drives chemo- and radiotherapy resistance in cancers.
  • Non-apoptotic programmed cell death (PCD) offers an alternative therapeutic strategy for apoptosis-resistant malignancies.

Purpose of the Study:

  • To investigate metformin's potential to induce pyroptosis in esophageal squamous cell carcinoma (ESCC).
  • To elucidate the molecular mechanisms underlying metformin-induced pyroptosis in ESCC, focusing on the PELP1 oncogene and the miR-497/PELP1 axis.

Main Methods:

  • In vitro and in vivo studies using ESCC models.
  • Assessment of metformin's effect on pyroptosis induction.
  • Analysis of proline-, glutamic acid- and leucine-rich protein-1 (PELP1) expression and its role in pyroptosis.
  • Investigation of the miR-497/PELP1 axis in metformin's mechanism of action.

Main Results:

  • Metformin effectively induces gasdermin D (GSDMD)-mediated pyroptosis in ESCC.
  • Upregulated PELP1 abrogates metformin-induced pyroptosis.
  • Metformin targets the miR-497/PELP1 axis to promote pyroptosis in ESCC.

Conclusions:

  • Metformin can induce pyroptosis in chemo-refractory esophageal squamous cell carcinoma.
  • Targeting the miR-497/PELP1 axis is a key mechanism for metformin-induced pyroptosis.
  • Metformin and other pyroptosis inducers represent potential alternative treatments for refractory cancers.
Keywords:
Chemotherapy resistanceGSDMDMetforminPyroptosismiR-497

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