Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632☆

摘要: Intrahepatic metastasis is one of the most important prognostic factors for patients with hepatocellular carcinoma (HCC). Cell motility mediated by Rho- and p160 Rho-associated coiledcoil forming protein kinase (p160ROCK) signaling pathways has recently been shown to play a critical role in intrahepatic human HCC. Furthermore, stable introduction dominant-negative p160ROCK into Li7 cells resulted reduced metastatic rate mice severe combined immunodeficiency (SCID). To investigate whether specific inhibitor, Y-27632, could also inhibit metastasis, effect Y-27632 on cell was investigated. markedly blocked actin reorganization lysophosphatidic acid (LPA). administered continuously peritoneal cavity using micro-osmotic pump, together orthotopic implantation liver SCID mice. Phosphate-buffered saline (PBS) alone as control. The incidence nodules decreased Y-27632-treated group. primary tumor volume at site injection smaller group compared control group, but difference not statistically significant. Histologically, tumors showed infiltrative growth sinusoidal area boundary, whereas expansive low invasiveness. These findings confirm importance Rho/p160ROCK pathway HCC, indicate that may be useful prevention