Related Experiment Video

Updated: Jul 1, 2025

Development of Compendium for Esophageal Squamous Cell Carcinoma
03:36

Development of Compendium for Esophageal Squamous Cell Carcinoma

Published on: April 12, 2024

411

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway

Wei-Feng Xia1, Xiao-Li Zheng2, Wen-Yi Liu2

  • 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Cancer Gene Therapy
|March 14, 2024
PubMed

Insights

Romidepsin, a histone deacetylase inhibitor, shows promise for treating esophageal squamous cell carcinoma (ESCC). This drug reduced cancer cell viability and tumor growth in preclinical models, offering a potential new therapy for ESCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly cancer with limited treatment options.
  • There is a critical need for novel therapeutic agents to combat ESCC.
  • Targeting cellular pathways offers a promising avenue for developing new anti-cancer drugs.

Purpose of the Study:

  • To identify novel compounds with anti-ESCC activity using high-throughput drug screening.
  • To investigate the therapeutic potential of romidepsin in preclinical models of ESCC.
  • To elucidate the molecular mechanisms underlying romidepsin's anti-ESCC effects.

Main Methods:

  • High-throughput drug screening (HTS) of compounds against ESCC cell lines in 2D and 3D cultures.
  • In vitro assays assessing cell viability, apoptosis, and cell cycle progression.
  • In vivo studies using ESCC cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models.
  • Molecular analyses including gene expression and pathway analysis (mTORC1).

Main Results:

  • Romidepsin was identified as a potent anti-ESCC agent through HTS.
  • Romidepsin decreased ESCC cell viability, induced apoptosis, and caused cell cycle arrest.
  • Romidepsin upregulated DDIT4 gene expression via histone hyperacetylation, inhibiting the mTORC1 pathway.
  • Romidepsin demonstrated superior efficacy and safety compared to conventional drugs in PDX models.

Conclusions:

  • Romidepsin is a promising candidate for esophageal squamous cell carcinoma therapy.
  • The drug's mechanism involves DDIT4 induction and mTORC1 inhibition.
  • Romidepsin shows potential as a novel therapeutic option for ESCC patients.

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