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Targeting ornithine decarboxylase (ODC) inhibits esophageal squamous cell carcinoma progression

Wei He1,2,3,4, Eunmiri Roh1, Ke Yao1

  • 11The Hormel Institute, University of Minnesota, Austin, MN 55912 USA.

NPJ Precision Oncology
|June 7, 2018
PubMed

Insights

Ornithine decarboxylase (ODC) is elevated in esophageal squamous cell carcinoma (ESCC). Inhibiting ODC with difluoromethylornithine suppressed ESCC cell growth and tumor development in preclinical models.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Esophageal squamous cell carcinoma (ESCC) is a significant global health concern.
  • Ornithine decarboxylase (ODC) plays a crucial role in cell proliferation and cancer development.
  • Understanding ODC's role in ESCC is vital for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of ornithine decarboxylase (ODC) in the progression of esophageal squamous cell carcinoma (ESCC).
  • To evaluate the therapeutic potential of targeting ODC using difluoromethylornithine (DFMO) in ESCC.

Main Methods:

  • Immunohistochemistry and Western blot analysis were used to assess ODC expression in ESCC cell lines and tissues.
  • shRNA-mediated ODC knockdown and treatment with the ODC inhibitor difluoromethylornithine (DFMO) were employed in vitro.
  • A patient-derived xenograft mouse model of ESCC was utilized to assess the in vivo efficacy of DFMO.

Main Results:

  • ODC protein expression was significantly higher in ESCC tissues compared to normal or inflamed esophageal tissues.
  • ODC depletion using shRNA led to G2/M cell cycle arrest and apoptosis in ESCC cells, inhibiting tumorigenesis.
  • In vivo treatment with DFMO reduced ESCC tumor size and weight by decreasing proliferation and inducing apoptosis.

Conclusions:

  • Ornithine decarboxylase is upregulated in ESCC and contributes to its progression.
  • Targeting ODC with difluoromethylornithine demonstrates significant preclinical antitumor activity against ESCC.
  • Difluoromethylornithine shows promise as a therapeutic agent for esophageal squamous cell carcinoma and warrants further clinical investigation.

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