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 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.
Routhier
Alissa
A
Ghosh Science and Technology Center, Department of Biology, Worcester State College, Worcester, MA 01602, USA.
Astuccio
Michelle
M
Lahey
Deanna
D
Monfredo
Nicholas
N
Johnson
Alyssa
A
Callahan
William
W
Partington
Amy
A
Fellows
Kelly
K
Ouellette
Lori
L
Zhidro
Sofiela
S
Goodrow
Carrie
C
Smith
Alexis
A
Sullivan
Kaitlyn
K
Simone
Peter
P
Le
Leo
L
Vezuli
Bora
B
Zohni
Micheline
M
West
Elizabeth
E
Gleason
Daniel
D
Bryan
Brad
B
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
D000577:Amides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases