The Rho-kinase inhibitor HA-1077 suppresses proliferation-migration and induces apoptosis of urothelial cancer cellsReportar como inadecuado




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BMC Cancer

, 14:412

Experimental therapeutics and drug development

Abstract

BackgroundActivation 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.

MethodsWe 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.

ResultsLysophosphatidic 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.

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

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-412 contains supplementary material, which is available to authorized users.

Hideyuki Abe, Takao Kamai contributed equally to this work.

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Autor: Hideyuki Abe - Takao Kamai - Keitaro Hayashi - Naohiko Anzai - Hiromichi Shirataki - Tomoya Mizuno - Yoshiyuki Yamaguchi -

Fuente: https://link.springer.com/







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