RT Journal Article SR Electronic T1 SK-216, an inhibitor of plasminogen activator inhibitor-1, limits tumor growth and lung metastasis formation probably through the reduction of tumor angiogenesis JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP p1479 VO 38 IS Suppl 55 A1 Takeshi Masuda A1 Noboru Hattori A1 Kousuke Hamai A1 Shin Akita A1 Tadashi Senoo A1 Hiroshi Iwamoto A1 Shinichiro Ohshimo A1 Masashi Kanehara A1 Nobuhisa Ishikawa A1 Kazunori Fujitaka A1 Yoshinori Haruta A1 Hiroshi Murai A1 Nobuoki Kohno YR 2011 UL http://erj.ersjournals.com/content/38/Suppl_55/p1479.abstract AB Introduction: Plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of plasminogen activators, is known to be involved in tumor progression.Objectives: To investigate whether a PAI-1 inhibitor, SK-216, can limit tumor growth and lung metastasis formation.Methods: C57BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma (LLC) cells and tumor volume (mm3) was measured twice a week until 2 weeks after the inoculation. The numbers of lung tumors were also counted 21 days after the injection of LLC cells through the tail vein. The mice were given either water or SK-216 (500 p.p.m.) in drinking water. In addition, the sections of tumor were stained with CD31 antibody, and the number of CD31-positive vessels was counted in three random microscopic fields per section.Results: The volumes of subcutaneous tumors 14 days after the inoculation of LLC cells were significantly smaller in SK-216-treated group than those in control group (mean ± SD; 1566±515.9 and 2354.3±559.3, respectively; p=0.018). The numbers of lung surface tumors were significantly lower in SK-216-treated group than those in control group (3.3±4.1 and 12.1±7.3, respectively; p=0.02). The numbers of CD31-positive vessels in subcutaneous or lung tumor sections were significantly lower in SK-216-treated group than those in control group (subcutaneous tumor; 60.5±15.9/field and 78.7±21.8/field, respectively, p=0.004: lung tumor; 24.0±7.9/field and 44.8±4.4/field, respectively, p=0.002).Conclusion: These results suggest that SK-216 limits tumor growth and lung metastasis formation probably through the reduction of tumor angiogenesis.