Selective activation of PPARγ inhibits pancreatic cancer invasion and decreases expression of tissue plasminogen activator

Background. PPARγ is a ligand-activated transcription factor with antitumor effects; its ability to inhibit pancreatic cancer invasion is unknown. The purpose of this study was to define the inhibitory effect of PPARγ ligands on pancreatic cancer invasion and the expression of invasion-related genes. Methods. Western blotting was used to establish expression of PPARγ in AsPC-1 and SUIT-2 cells. AsPC-1 cells were treated with nontoxic doses of PPARγ ligands (15d-PGJ₂, troglitazone, or rosiglitazone) and Matrigel Invasion chambers were used to assess invasion in vitro. A microarray for genes that contribute to invasion was used to investigate the antiinvasive targets of PPARγ. Gene array results were confirmed by use of ribonuclease protection assay or Northern blotting. Results. Rosiglitazone and 15d-PGJ₂ decreased AsPC-1 cell invasion; GW9662, which inhibits PPARγ, reversed this effect. The expression of tissue plasminogen activator (tPA) was decreased by rosiglitazone treatment, which was confirmed by Northern blotting. Secreted levels of tPA in AsPC-1 conditioned media were also decreased. Conclusions. We demonstrate, for the first time, that secretion of the invasive factor tPA was decreased by rosiglitazone treatment in AsPC-1 cells. PPARγ ligands inhibit pancreatic cancer cell invasion, suggesting that these agents may represent novel strategies to treat pancreatic cancer.