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

Satsuki Mashiko, Kazuyuki Kitatani, Masafumi Toyoshima, Atsuhiko Ichimura, Takashi Dan, Toshinori Usui, Masumi Ishibashi, Shogo Shigeta, Satoru Nagase, Toshio Miyata, Nobuo Yaegashi

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

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 antitumor agents.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalCancer Biology and Therapy
Volume16
Issue number2
DOIs
Publication statusPublished - 2015 Feb 1

Keywords

  • Cancer therapeutics
  • Clear cell carcinoma of the ovary
  • Ovarian cancer
  • Plasminogen activator inhibitor-1
  • Plasminogen activator inhibitor-1 inhibitor
  • TM5275

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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