PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. Academic Article uri icon

Overview

abstract

  • Several drugs approved for a variety of indications have been shown to exhibit antiangiogenic effects. Our study focuses on the PPARgamma ligand rosiglitazone, a compound widely used in the treatment of type 2 diabetes. We demonstrate, for the first time to our knowledge, that PPARgamma is highly expressed in tumor endothelium and is activated by rosiglitazone in cultured endothelial cells. Furthermore, we show that rosiglitazone suppresses primary tumor growth and metastasis by both direct and indirect antiangiogenic effects. Rosiglitazone inhibits bovine capillary endothelial cell but not tumor cell proliferation at low doses in vitro and decreases VEGF production by tumor cells. In our in vivo studies, rosiglitazone suppresses angiogenesis in the chick chorioallantoic membrane, in the avascular cornea, and in a variety of primary tumors. These results suggest that PPARgamma ligands may be useful in treating angiogenic diseases such as cancer by inhibiting angiogenesis.

authors

  • Panigrahy, Dipak
  • Singer, Samuel
  • Shen, Lucy Q
  • Butterfield, Catherine E
  • Freedman, Deborah A
  • Chen, Emy J
  • Moses, Marsha A
  • Kilroy, Susan
  • Duensing, Stefan
  • Fletcher, Christopher
  • Fletcher, Jonathan A
  • Hlatky, Lynn
  • Hahnfeldt, Philip
  • Folkman, Judah
  • Kaipainen, Arja

publication date

  • October 1, 2002

Research

keywords

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Neoplasm Metastasis
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors

Identity

PubMed Central ID

  • PMC151148

Scopus Document Identifier

  • 0036771776

Digital Object Identifier (DOI)

  • 10.1172/JCI15634

PubMed ID

  • 12370270

Additional Document Info

volume

  • 110

issue

  • 7