Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer

Plasminogen activator inhibitor (PAI)-1 is predictive of poor outcome in several types of Cancer. The present study investigated the biological role for PAI-1 in ovarian Cancer and potential of targeted pharmacotherapeutics. In patients with ovarian Cancer, PAI-1 mRNA expression in tumor tissues was positively correlated with poor prognosis. To determine the role of PAI-1 in cell proliferation in ovarian Cancer, the effects of PAI-1 inhibition were examined in PAI-1-expressing ovarian Cancer cells. PAI-1 knockdown by small interfering RNA resulted in significant suppression of cell growth accompanied with G2/M cell cycle arrest and intrinsic Apoptosis. Similarly, treatment with the small molecule PAI-1 Inhibitor TM5275 effectively blocked cell proliferation of ovarian Cancer cells that highly express PAI-1. Together these results suggest that PAI-1 promotes cell growth in ovarian Cancer. Interestingly, expression of PAI-1 was increased in ovarian clear cell carcinoma compared with that in serous tumors. Our results suggest that PAI-1 inhibition promotes cell cycle arrest and Apoptosis in ovarian Cancer and that PAI-1 inhibitors potentially represent a novel class of anti-tumor agents.