title: u-PA inhibitor amiloride suppresses peritoneal metastasis in gastric cancer.
abstract: BACKGROUND
  Peritoneal metastasis in gastric cancer represents a ubiquitous human health problem but effective therapies with limited side effects are still lacking. Although previous research suggested that u-PA was involved in some tumor metastasis such as lung-specific metastasis, the role of u-PA for peritoneal metastasis in gastric cancer is still unclear. The aim of this study was to explore whether selective pharmacological blockade of u-PA is able to affect the peritoneal metastasis of gastric cancer both in vivo and in vitro.
  
  
  METHODS
  In the present study, we evaluated the effects and explored the anti-tumor mechanisms of amiloride, a selective u-PA inhibitor, on a panel of gastric cancer cell lines and in a murine model of human gastric cancer MKN45.
  
  
  RESULTS
  The study showed that amiloride significantly inhibited the tumor growth and prolonged the survival of the tumor-bearing mice. In vitro, compared with controls, amiloride could not only significantly down-regulate the mRNA expression and protein level of u-PA from MKN45 cells with dose dependence but also inhibit the adhesion of HMrSV5 cells, migration and invasion of MKN45 cells.
  
  
  CONCLUSIONS
  The findings in our current report provide evidence that selective u-PA inhibitor amiloride has potent effects against peritoneal metastasis in gastric cancer, suggesting its possible therapeutic value for the treatment of gastric cancer.
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Road II, Shanghai 200025, China.
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Ding
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Zhou
authors.forename: Mingan
authors.initials: M
authors.lastname: Zhong
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Chen
authors.forename: Xujing
authors.initials: X
authors.lastname: Wang
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000627:therapeutic use*; D000584:Amiloride / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D012333:RNA, Messenger; D000584:Amiloride; D014568:Urokinase-Type Plasminogen Activator