Open Access Highly Accessed Research article

The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells

Hideyuki Abe1, Takao Kamai1*, Keitaro Hayashi2, Naohiko Anzai2, Hiromichi Shirataki3, Tomoya Mizuno1, Yoshiyuki Yamaguchi1, Akinori Masuda1, Hideo Yuki1, Hironori Betsunoh1, Masahiro Yashi1, Yoshitatsu Fukabori1 and Ken-Ichiro Yoshida1

Author Affiliations

1 Department of Urology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan

2 Department of Pharmacology and Toxicology, Dokkyo Medical University, Mibu, Tochigi, Japan

3 Department of Molecular and Cell Biology, Dokkyo Medical University, Mibu, Tochigi, Japan

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BMC Cancer 2014, 14:412  doi:10.1186/1471-2407-14-412

Published: 7 June 2014



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.


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.


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.


These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.