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Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model

Jerena Manoharan1, Volker Fendrich2, Pietro Di Fazio2

  • 1Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germanyjerena_manoharan@outlook.com.

Neuroendocrinology
|July 20, 2018
PubMed

Insights

Aspirin and enalapril significantly reduced pancreatic neuroendocrine neoplasia (pNET) size and number in a mouse model of multiple endocrine neoplasia type 1 (MEN1). These findings suggest potential chemopreventive strategies for MEN1-associated pNETs.

Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • Pancreatic neuroendocrine neoplasias (pNEN) are the leading cause of mortality in multiple endocrine neoplasia type 1 (MEN1) patients.
  • Limited chemopreventive options exist for MEN1-associated pNENs, necessitating research into novel therapeutic strategies.

Purpose of the Study:

  • To evaluate aspirin and enalapril as single chemopreventive agents for pNENs in a mouse model of MEN1.
  • To assess the impact of these agents on pNEN size, number, apoptosis, and molecular markers.

Main Methods:

  • A transgenic Men1(+/T) knockout mouse model was used, with 75 mice divided into three groups: aspirin, enalapril, and control.
  • Mice were treated for up to 18 months, with pancreata analyzed via histopathology, immunostaining, and real-time PCR at various intervals.
  • Measurements included pNEN size, number, apoptosis marker (caspase 3), VEGF expression, and RELA transcript levels.

Main Results:

  • Both aspirin and enalapril significantly reduced pNEN size by approximately 80% and decreased the number of pNENs by 33% and 41%, respectively.
  • Increased caspase 3 expression and decreased VEGF expression were observed in treated mice.
  • Enalapril significantly downregulated RELA transcript at 18 months, while aspirin did not show this effect. Ki-67 index remained unchanged.

Conclusions:

  • Aspirin and enalapril demonstrate significant efficacy as chemopreventive agents against pNENs in a MEN1 mouse model.
  • These drugs show potential for reducing pNEN progression and warrant further investigation for clinical application in MEN1 patients.
  • The study provides the first evidence for aspirin and enalapril as effective chemopreventive agents for pNENs in a relevant preclinical model.
Keywords:
AspirinChemopreventionEnalaprilMultiple endocrine neoplasia type 1

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