The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells
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- 作者：Hideyuki Abe (1)
Takao Kamai (1)
Keitaro Hayashi (2)
Naohiko Anzai (2)
Hiromichi Shirataki (3)
Tomoya Mizuno (1)
Yoshiyuki Yamaguchi (1)
Akinori Masuda (1)
Hideo Yuki (1)
Hironori Betsunoh (1)
Masahiro Yashi (1)
Yoshitatsu Fukabori (1)
Ken-Ichiro Yoshida (1)
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 - 刊名：BMC Cancer
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：14
- 期：1
- 全文大小：2,683 KB
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48. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/412/prepub - 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
- 出版者：BioMed Central
- ISSN：1471-2407
文摘
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.