Peroxisome-proliferator-activated receptors γ and β/δ mediate vascular endothelial growth factor production in colorectal tumor cells

Clemens Röhrl, Ulrike Kaindl, Inga Koneczny, Xenia Hudec, David M. Baron, Jürgen S. König, Brigitte Marian

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Background: Peroxisome-proliferator-activated receptors (PPARs) are nuclear receptors for fatty acids and their derivatives. PPAR subtypes PPARγ and PPARβ/δ are suspected to modulate cancer development in the colon, but their exact role is still discussed controversially. Methods: The present study investigated the impact of PPARγ and PPARβ/δ on vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX-2) expressions induced by synthetic and physiological agonists in the colorectal tumor cell lines SW480 and HT29 using reporter gene assays, qRT-PCR and ELISA. Results: Activation of both PPARγ and PPARβ/δ induced expression of VEGF mRNA and protein in a PPAR-dependent way. The PPARγ agonists ciglitazone and PGJ2 were the most effective inducers with up to ninefold and threefold increases in VEGF mRNA in SW480 and HT29 cultures, respectively. VEGF secretion was doubled in both cell lines. The PPARβ/δ agonists GW501516 and PGI2 caused stimulations of only 1.5-fold in both cell lines. In addition, all PPAR agonists induced COX-2 mRNA and secretion of the COX-2 product PGE2 in HT29 cells. However, this effect was not blocked by knock-down of PPAR expression nor was it essential for VEGF expression as shown by the lack of effect of the COX-2 inhibitor SC236. Conclusion: In summary, our results identify both PPARγ and PPARβ/δ as an alternative COX-independent mechanism of VEGF induction in colorectal tumor cells.

Original languageEnglish
Pages (from-to)29-39
Number of pages11
JournalJournal of Cancer Research and Clinical Oncology
Volume137
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Keywords

  • Colon cancer
  • COX-2
  • PPAR
  • VEGF
  • Thiazoles/pharmacology
  • Humans
  • PPAR gamma/agonists
  • Colorectal Neoplasms/genetics
  • PPAR-beta/agonists
  • Vascular Endothelial Growth Factor A/biosynthesis
  • Cyclooxygenase 2/genetics
  • RNA, Messenger/metabolism
  • PPAR delta/agonists
  • Thiazolidinediones/pharmacology
  • Peroxisome Proliferator-Activated Receptors/agonists
  • Cell Line, Tumor

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