Rho-associated kinase inhibitor, Y-27632, inhibits the invasion and proliferation of T24 and 5367 bladder cancer cells

摘要

The serine/threonine kinases, Rho-associated protein kinase I and II (ROCK I and II), regulate the cytoskeleton by acting downstream of the small GTPase, Rho, and have been implicated in tumorigenesis and cancer metastasis. Inhibition of ROCK signaling has been shown to suppress the invasion and migration of several types of cancer cells. In this study, the effect of the ROCK inhibitor, Y-27632, on the proliferation and invasion of T24 and 5637 bladder cancer cells was investigated. In the proliferation assays, the cells were exposed to 0, 10, 25, 50, 75, 100, 125 or 150 mu mol/l Y-27632 and proliferation was determined using Cell Counting kit-8 after 24, 48 and 72 h. In the invasion assays, the cells were placed in the upper chamber of transwell plates and subjected to 0, 25, 50 or 75 mu mol/l Y-27632 for 24 h, after which invasion was measured. Y-27632 significantly suppressed the cell proliferation of T24 and 5637 cells in a concentration- and time-dependent manner. Y-27632 also inhibited the invasion of T24 and 5637 cells in a concentration-dependent manner (P<0.001). In addition, Y-27632 suppressed myosin light chain kinase (MLCK) phosphorylation in T24 and 5637 cells, confirming that it is also a downstream effector of the Rho/ROCK pathway in T24 and 5637 bladder cancer cells. In conclusion, the Rho/ROCK/P-MLCK pathway may be important in tumor cell metastasis in bladder cancer.