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

Primarily through in vitro studies, the Rho-family of small GTPases and their effector proteins have been impli- cated 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.