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Corynoline inhibits esophageal squamous cell carcinoma growth via targeting Pim-3

Yunshu Shi1, Qiang Yuan1, Yingying Chen2

  • 1The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450000, China; Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan 450052, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|December 21, 2023
PubMed
Abstract

Insights

Proviral integration site for Maloney murine leukemia virus 3 (Pim-3) drives esophageal squamous cell carcinoma (ESCC) growth. Corynoline effectively inhibits ESCC progression by targeting Pim-3, offering a potential new therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with poor survival rates.
  • Current therapies for ESCC often face resistance, highlighting the need for novel therapeutic targets.
  • Identifying key oncogenic drivers and effective inhibitors is crucial for advancing ESCC treatment.

Purpose of the Study:

  • To investigate the role of proviral integration site for Maloney murine leukemia virus 3 (Pim-3) in ESCC.
  • To evaluate corynoline as a potential therapeutic agent targeting Pim-3 in ESCC.
  • To elucidate the molecular mechanisms by which corynoline inhibits ESCC progression.

Main Methods:

  • Immunohistochemistry was used to assess Pim-3 protein levels in ESCC tissues.
  • Cell proliferation assays (MTT, colony formation) were employed to study Pim-3 function.
  • Biochemical assays (computer docking, pull-down, CTSA, kinase assay) confirmed corynoline-Pim-3 interaction and inhibition.
  • Western blotting and a patient-derived xenograft model were utilized to explore the inhibitory mechanism.

Main Results:

  • Pim-3 was found to be highly expressed in ESCC and promoted cell proliferation and tumor development.
  • Pim-3 enhanced ESCC growth by phosphorylating mitogen-activated protein kinase 1 (MAPK1).
  • Corynoline directly bound to Pim-3, inhibiting its kinase activity and suppressing ESCC growth, leading to apoptosis.

Conclusions:

  • Pim-3 is a significant promoter of ESCC progression.
  • Corynoline demonstrates efficacy in inhibiting ESCC by targeting Pim-3.
  • Targeting Pim-3 with agents like corynoline represents a promising therapeutic strategy for ESCC.
Keywords:
ApoptosisCorynolineEsophageal squamous cell carcinomaProliferationProviral integration site for maloney murine leukemia virus 3

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