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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Hideyuki Abe, Takao Kamai, Keitaro Hayashi, Naohiko Anzai, Hiromichi Shirataki, Tomoya Mizuno, Yoshiyuki Yamaguchi, Akinori Masuda, Hideo Yuki, Hironori Betsunoh, Masahiro Yashi, Yoshitatsu Fukabori, Ken-Ichiro Yoshida

Published in: BMC Cancer | Issue 1/2014

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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.
Appendix
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Metadata
Title
The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells
Authors
Hideyuki Abe
Takao Kamai
Keitaro Hayashi
Naohiko Anzai
Hiromichi Shirataki
Tomoya Mizuno
Yoshiyuki Yamaguchi
Akinori Masuda
Hideo Yuki
Hironori Betsunoh
Masahiro Yashi
Yoshitatsu Fukabori
Ken-Ichiro Yoshida
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-412

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