期刊
CANCER BIOLOGY & THERAPY
卷 16, 期 2, 页码 253-260出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2014.1001271
关键词
cancer therapeutics; clear cell carcinoma of the ovary; ovarian cancer; plasminogen activator inhibitor-1; plasminogen activator inhibitor-1 inhibitor; TM5275
类别
资金
- JSPS KAKENHI [23790366, 24390375, 23791801]
- Health Labor Sciences Research Grant [201221019A]
- Kurokawa Cancer Research Foundation
- Japan Society of Gynecologic Oncology
- Foundation for Promotion of Cancer Research
- Tohoku University Graduate School of Medicine United Center for Advanced Research and Translational Medicine
- Grants-in-Aid for Scientific Research [23791801, 24390375, 23790366] Funding Source: KAKEN
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.
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