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Related Experiment Videos

Y2 receptors decrease human pancreatic cancer growth and intracellular cyclic adenosine monophosphate levels

C D Liu1, L W Slice, A Balasubramaniam

  • 1Department of Surgery, University of California-Los Angeles Center for the Health Sciences, USA.

Surgery
|August 1, 1995
PubMed
Summary

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BIM-43004-1, a Y2 receptor agonist, significantly reduced pancreatic cancer growth in mice by decreasing cAMP levels. This synthetic peptide shows promise for treating pancreatic adenocarcinoma.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Peptide YY (PYY) is an enteric hormone that inhibits pancreatic function.
  • Previous research indicated BIM-43004-1, a PYY analog, reduced mitochondrial activity in pancreatic cancer cells.
  • The in vivo effects of PYY and BIM-43004-1 on pancreatic cancer growth were unexplored.

Purpose of the Study:

  • To investigate the effects of PYY and BIM-43004-1 on pancreatic cancer growth in vivo.
  • To assess the impact of these agents on tumor mass and receptor binding.
  • To determine changes in intracellular cyclic adenosine monophosphate (cAMP) levels.

Main Methods:

  • Human pancreatic cancer cells (Mia PaCa-2) were orthotopically transplanted into athymic mice.
  • Mice received PYY or BIM-43004-1 (200 pmol/kg/hr) or saline via miniosmotic pumps for 2-4 weeks.

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  • Tumor mass, receptor binding, and intracellular cAMP levels were measured.

    • Main Results:

    • BIM-43004-1 treatment decreased tumor mass by 60.5%, while PYY decreased it by 27.1%.
    • Receptor binding studies quantified BIM-43004-1 binding affinity (Kd=4.5 nmol) and receptor density (27,000 receptors/cell).
    • BIM-43004-1 reduced intracellular cAMP by 52.5%, compared to 15.3% for PYY.

    Conclusions:

    • BIM-43004-1, a Y2 agonist, binds to pancreatic cancer cells and suppresses tumor growth in vivo.
    • The compound reduces intracellular cAMP levels, contributing to its anti-tumor effect.
    • Adjuvant therapy with BIM-43004-1 may benefit pancreatic adenocarcinoma patients.