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AIM:Intrahepatic extension is the main cause of liver failureand death in hepatocellular carcinoma patients.The smallGTPase Rho and one of its effector molecules ROCK regulatecytoskeleton and actomyosin contractility,and play a crucialrole in cell adhesion and motility.We investigated the roleof small GTPase Rho in biological behaviors of hepatocellularcarcinoma to demonstrate the importance of Rho in cancerinvasion and metastasis.METHODS:Using Western blotting,we quantitated Rhoprotein expression in SMMC-7721 cells induced byLysophosphatidic acid (LPA).Furthermore,we examined therole of Rho signaling in regulating the motile and invasiveproperties of tumor cells.RESULTS:Rho protein expression was stimulated by LPA.Using the Rhotekin binding assay to assess Rho activation,we observed that the level of GTP-bound Rho was elevatedtransiently alter the addition of LPA,and Y-27632 decreasedthe level of active Rho.LPA enhanced the motility of tumorcells and facilitated their invasion.Rho played an essentialrole in the migratory process,as evidenced by the inhibitionof migration and motility of cancer cells by a specific inhibitorof ROCK,Y-27632.CONCLUSION:The finding that invasiveness of hepatocellularcarcinoma is facilitated by the Rho/Rho-kinase pathway islikely to be relevant to tumor progression and Y-27632 maybe a new potential effective agent for the prevention ofintrahepatic extension of human liver cancer.
AIM: Intrahepatic extension is the main cause of liver failure and death in hepatocellular carcinoma patients. The small GTPase Rho and one of its effector molecules ROCK regulate cytoskeleton and actomyosin contractility, and play a crucial role in cell adhesion and motility. We investigated the role of small GTPase Rho in biological behaviors of hepatocellularcarcinoma to demonstrate the importance of Rho in cancer invasion and metastasis. METHODS: Using Western blotting, we quantitated Rhoprotein expression in SMMC-7721 cells induced byLysophosphatidic acid (LPA). Frthermore, we examined the course of Rho signaling in regulating the motile and PCR assays of the level of GTP-bound Rho was elevated transiently the addition of LPA, and Y-27632 decreasedthe level of active Rho.LPA enhanced the motility of tumor cells and facilitated their invasion. Rho pla yed an essentialrole in the migratory process, as evidenced by the inhibition of migration and motility of cancer cells by a specific inhibitor of ROCK, Y-27632. CONCLUSION: The finding that invasiveness of hepatocellular carcinoma is facilitated by the Rho / Rho-kinase pathway is likely to be relevant to tumor progression and Y-27632 maybe a new potential effective agent for the prevention of intrahepatic extension of human liver cancer.