Pharmacological inhibition of Rho-kinase signaling with Y-27632 blocks melanoma tumor growth.

Abstract:

:Primarily through in vitro studies, the Rho-family of small GTPases and their effector proteins have been implicated in mediating oncogenic properties of cancer cells. We sought to determine if pharmacological inhibition of the RhoA effector proteins known as Rho-kinases (ROCK) with the small molecule inhibitor Y-27632 could inhibit melanoma in vitro and in vivo. We demonstrate that Y-27632 treatment of a panel of melanoma cells alters cellular morphology leading to spindly cells with decreased lamellipodia and increased filopodia formation. Y-27632 treatment decreases invasion and alters cell survival of cultured melanoma cells. IP injection of Y-27632 in tumor-bearing mice resulted in a reduction in melanoma tumor volume compared to control treated mice. These findings suggest that ROCK inhibition can reduce melanoma tumorigenicity.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Routhier A,Astuccio M,Lahey D,Monfredo N,Johnson A,Callahan W,Partington A,Fellows K,Ouellette L,Zhidro S,Goodrow C,Smith A,Sullivan K,Simone P,Le L,Vezuli B,Zohni M,West E,Gleason D,Bryan B

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

861-7

issue

3

eissn

1021-335X

issn

1791-2431

journal_volume

23

pub_type

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