Activation of Peroxisome Proliferator-Activated Receptor Gamma Inhibits the Growth of Human Pancreatic Cancer

Objective: In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ was analyzed with reverse transcription-polymerase chain reaction and immunoblotting. The interaction between PPARγ 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: PPARγ 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 PPARγ plays an important role in human pancreatic cancer growth and that ligand-induced activation of PPARγ would be a useful strategy for treatment of human pancreatic cancer.