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Controversy: PPARgamma as a target for treatment of colorectal cancer

Rajnish A Gupta1, Raymond N Dubois

  • 1Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

American Journal of Physiology. Gastrointestinal and Liver Physiology
|July 18, 2002
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPARgamma) shows potential in colorectal cancer (CRC) treatment. While it inhibits cancer cell growth, its role in tumor development requires further investigation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Colorectal cancer (CRC) is a major global health concern.
  • Nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) ligands show therapeutic promise for CRC.
  • PPARgamma's role in CRC development is complex and debated.

Purpose of the Study:

  • To investigate the role of PPARgamma in colorectal cancer.
  • To reconcile conflicting data regarding PPARgamma's effect on tumor formation.

Main Methods:

  • In vitro studies using cultured CRC cells.
  • In vivo studies using nude mouse xenograft models.
  • In vivo studies using carcinogen-induced rat models of CRC.
  • In vivo studies using APC(Min) mice models of intestinal polyposis.
  • Analysis of human CRC specimens for PPARgamma mutations.

Main Results:

  • PPARgamma activation reduced proliferation of CRC cells in vitro and in vivo.
  • PPARgamma agonists decreased preneoplastic lesions in a rat CRC model.
  • PPARgamma ligands paradoxically increased adenoma formation in APC(Min) mice.
  • Genetic studies revealed loss-of-function PPARgamma mutations in human CRC specimens.

Conclusions:

  • PPARgamma activation demonstrates anti-proliferative effects on colorectal cancer cells.
  • PPARgamma likely acts as a tumor suppressor in colorectal cancer development.
  • Discrepancies in APC(Min) mouse models may stem from model limitations.
  • Further research is warranted to fully elucidate PPARgamma's therapeutic potential in CRC.

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