title: 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.
authors.affiliation: Ghosh Science and Technology Center, Department of Biology, Worcester State College, Worcester, MA 01602, USA.
authors.forename: Alissa
authors.initials: A
authors.lastname: Routhier
authors.forename: Michelle
authors.initials: M
authors.lastname: Astuccio
authors.forename: Deanna
authors.initials: D
authors.lastname: Lahey
authors.forename: Nicholas
authors.initials: N
authors.lastname: Monfredo
authors.forename: Alyssa
authors.initials: A
authors.lastname: Johnson
authors.forename: William
authors.initials: W
authors.lastname: Callahan
authors.forename: Amy
authors.initials: A
authors.lastname: Partington
authors.forename: Kelly
authors.initials: K
authors.lastname: Fellows
authors.forename: Lori
authors.initials: L
authors.lastname: Ouellette
authors.forename: Sofiela
authors.initials: S
authors.lastname: Zhidro
authors.forename: Carrie
authors.initials: C
authors.lastname: Goodrow
authors.forename: Alexis
authors.initials: A
authors.lastname: Smith
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Sullivan
authors.forename: Peter
authors.initials: P
authors.lastname: Simone
authors.forename: Leo
authors.initials: L
authors.lastname: Le
authors.forename: Bora
authors.initials: B
authors.lastname: Vezuli
authors.forename: Micheline
authors.initials: M
authors.lastname: Zohni
authors.forename: Elizabeth
authors.initials: E
authors.lastname: West
authors.forename: Daniel
authors.initials: D
authors.lastname: Gleason
authors.forename: Brad
authors.initials: B
authors.lastname: Bryan
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007274:Injections, Intraperitoneal; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases