Peroxisome proliferator-activated receptor-γ inhibits pancreatic cancer cell invasion and metastasis via regulating MMP-2 expression through PTEN.

The invasive and metastatic behavior of pancreatic cancer is associated with a poor prognosis. Therefore, understanding the molecular mechanisms underlying the invasion and metastasis of pancreatic cancer has important application values theoretically and clinically. In previous years, with increasing studies focusing on tumor pathogenesis, it has been revealed that peroxisome proliferator‑activated receptor‑γ (PPARγ) and phosphatase and tensin homolog (PTEN) are closely associated with the occurrence and development of pancreatic cancer. Thus, in the present study, a scratch wound assay, western blotting and transwell assays were used to investigate their function. The scratch wound assay demonstrated that treatment with the PPARγ ligand rosiglitazone (RGZ) could reduce the movement and migration of pancreatic cancer cells. Western blotting results indicated that while RGZ inhibited the expression of matrix metalloproteinase (MMP)‑2, PPARγ inhibitors promoted MMP‑2 expression. However, PPARγ ligands and inhibitors did not affect the expression of MMP‑9. Further investigation indicated that the regulation of MMP‑2 by PPARγ activation occurred through PTEN. In addition, PPARγ activation promoted PTEN expression, thereby inhibiting the expression of MMP‑2. Subsequent transwell experiments demonstrated that RGZ treatment significantly inhibited the invasiveness of pancreatic cancer cells and the inhibitory effect of RGZ was completely reversed by simultaneous transfection of the MMP‑2‑overexpressing vector, which increased the invasiveness of pancreatic cancer cells. Therefore, PPARγ activation can activate PTEN expression, thereby suppressing the expression of MMP‑2 and hence inhibiting the invasion and metastasis of pancreatic cancer cells.