Activation of peroxisome proliferator-activated receptor gamma inhibits the growth of human pancreatic cancer

Pathobiology. 2001;69(5):258-65. doi: 10.1159/000064336.


Objective: In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human pancreatic cancer and the possible effects of its ligand engagement on cell growth.

Methods: Seven human pancreatic cancer cell lines and 7 surgically resected human pancreatic cancer tissues were used as samples. The expression of PPARgamma was analyzed with reverse transcription-polymerase chain reaction and immunoblotting. The interaction between PPARgamma and PPAR-responsive element (PPRE) was examined by gel shift assay. Growth inhibition by thiazolidinediones was confirmed with anchorage-dependent and anchorage-independent growth assays.

Results: PPARgamma was detected in all cell lines tested and in 5 out of 7 cancer tissues (71%), but was not found in adjacent normal pancreatic tissues. Gel shift analysis revealed that the proteins in nuclear extracts of the pancreatic cancer cell line PANC-1 specifically bind to the PPRE. Cell growth was significantly inhibited by treatment with troglitazone and rosiglitazone in a dose- and time-dependent manner (p < 0.01). In contrast, a nonfunctional metabolic analog of troglitazone did not affect cell growth.

Conclusion: These observations suggest that PPARgamma plays an important role in human pancreatic cancer growth and that ligand-induced activation of PPARgamma would be a useful strategy for treatment of human pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Chromans / pharmacology
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / analysis
  • Receptors, Cytoplasmic and Nuclear / biosynthesis*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rosiglitazone
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Troglitazone
  • Tumor Cells, Cultured / drug effects


  • Antineoplastic Agents
  • Chromans
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Troglitazone