Antitumoral effect of a selective Rho-kinase inhibitor Y-27632 against Ehrlich ascites carcinoma in mice

Background: The Rho proteins and Rho-kinase (ROCK) enzymes are responsible for signal transduction, and cause cell permeability, contractility, differentiation, migration, proliferation or apoptosis depending on cell types. All of these functions are vital for cancer initiation and progression. In this study, the preventive and protective effects of a selective ROCK inhibitor Y-27632 against Ehrlich ascites carcinoma in Swiss albino mice were investigated. Methods: Adult male albino mice were divided into five equal groups, and Y-27632 (0.1, 1, and 10 mg/kg) was given to groups as two steps; before (pre-carcinoma) and after inoculation of carcinoma cell suspensions (post-carcinoma). At the end of the experiments (at day 15), cardiac blood samples, the ascitic fluid, and intestinal specimens were collected for histopathology and biochemical investigation. Results: Significant decreases in the body weight and immunostaining scores in small and large intestine for ROCK2, preservation of serum glutathione (GSH) levels, and an increase in tumor level of nitric oxide were recorded in groups pretreated with Y-27632. However, treatment with Y-27632 after tumor inoculation did not affect body weight and ROCK2 immunostaining scores, increased serum MDA levels, and decreased GSH levels. Conclusions: This is the first study on the effectiveness of Y-27632 in this experimental tumor model. Our findings provided direct evidence for ROCK involvement in tumor development. These data suggest that pretreatment with Y-27632 has a protective effect against tumor formation. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.