Ghosh Science and Technology Center, Department of Biology, Worcester State College, Worcester, MA 01602, USA.
Oncol Rep. 2010 Mar;23(3):861-7.
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.
主要通过体外研究，Rho 家族的小 GTPases 及其效应蛋白已被牵连到介导癌细胞的致癌特性。我们试图确定 RhoA 效应蛋白（称为 Rho 激酶（ROCK））的小分子抑制剂 Y-27632 的药理学抑制是否可以抑制体外和体内黑色素瘤。我们证明 Y-27632 处理一组黑色素瘤细胞改变细胞形态，导致具有减少的片状伪足和增加的丝状伪足形成的梭形细胞。Y-27632 处理减少了培养的黑色素瘤细胞的侵袭并改变了细胞存活。在荷瘤小鼠中进行 Y-27632 的 IP 注射导致与对照处理的小鼠相比黑色素瘤肿瘤体积减少。这些发现表明 ROCK 抑制可以降低黑色素瘤的致瘤性。
