title: The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells.
abstract: BACKGROUND
  Activation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract.
  
  
  METHODS
  We investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms.
  
  
  RESULTS
  Lysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity.
  
  
  CONCLUSIONS
  These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Urology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. kamait@dokkyomed.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Kamai
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Shirataki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Akinori
authors.initials: A
authors.lastname: Masuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Yuki
authors.forename: Hironori
authors.initials: H
authors.lastname: Betsunoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yashi
authors.forename: Yoshitatsu
authors.initials: Y
authors.lastname: Fukabori
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay; D001749:Urinary Bladder Neoplasms / Q000378:metabolism; D014571:Urologic Neoplasms / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C049347:fasudil