Growth inhibition of esophageal squamous carcinoma cells by peroxisome proliferator-activated receptor-gamma ligands

J Lab Clin Med. 2002 Jul;140(1):17-26. doi: 10.1067/mlc.2002.125055.


The growth of human cancer cells expressing peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been reported to be inhibited by PPAR-gamma ligands. In esophageal squamous-cell carcinoma cell lines T.T, T.Tn, and EC-GI-10, we detected expression of PPAR-gamma and investigated the effects of PPAR-gamma ligands on these cell lines in vitro with the use of troglitazone, pioglitazone, and 15d-PGJ2. Marked growth inhibition by the PPAR-gamma ligands was observed in all cases. The growth-inhibitory effect was evidenced by a dose-dependent inhibition of deoxyribonucleic acid synthesis and was associated with altered cell-cycle progression manifesting G1 arrest. Cell-cycle arrest in T.Tn cells induced by troglitazone could be correlated with an increased level of cyclin-dependent kinase inhibitor p27(Kip1), p21(Cip1/Waf1), and p18(Ink4c). Moreover, troglitazone treatment increased the expression of interleukin-1 alpha, a multifunctional cytokine implicated in antitumor immunity. These findings suggest that troglitazone and other PPAR-gamma ligands have adjuvant or neoadjuvant therapeutic potentials in esophageal cancer.

MeSH terms

  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle / drug effects
  • Cell Division / physiology
  • Chromans / pharmacology*
  • DNA Replication / drug effects
  • Esophageal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Ligands
  • RNA, Messenger / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic*
  • Troglitazone
  • Tumor Cells, Cultured


  • Chromans
  • Ligands
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Troglitazone