Regulation of MMP-2 activity in response to treatment of $PPAR_γ$ agonists

Abstract

Metastasis is the main cause of death in cancer patients. Active matrix metalloproteinases (MMPs) play a key role in tumor invasion. Many studied have tried to examine the role of peroxisome proliferator-activated receptor γ (PPARγ) in cancer. But it is still a debatable issue. Here, we report for the first time that ciglitazone induced pro-MMP-2 activation through induction of memebrane type 1-MMP (MT1-MMP) expression and increased the invasiveness of tumor in HT1080 cell but not the other PPARγ agonists of thiazolidinedione (TZD) class. Ciglitazone activated strongly PPAR_γ. But MMP-2 activation was not relevant to PPAR_γ activation. To investigate the mechanism of MMP-2 activation by ciglitazone, various antioxidants and signal inhibitors are pre-treated. So, we find that ciglitazone induced pro-MMP-2 activation by the sustained production of $H_2O_2$. And it was also regulated by ERK/NF-κB pathway.