Rho-kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells

Biochem Biophys Res Commun. 2000 Mar 24;269(3):652-9. doi: 10.1006/bbrc.2000.2343.


The Rho-kinase inhibitor, Y-27632, inhibited in vitro chemotactic migration to bone marrow fibroblast conditioned media and metastatic growth in immune-compromised mice of highly invasive human prostatic cancer (PC3) cells. Y-27632 also reduced myosin light chain phosphorylation and markedly altered the morphology of cells that developed numerous processes containing microtubules. A strikingly different, rounded phenotype was induced by an inhibitor of myosin light chain kinase, ML9. The M(110-130) subunit of the myosin phosphatase that is regulated by Rho-kinase was present in PC3 cells that contained significantly more RhoA than the less invasive, LNCaP cells. Y-27632 also inhibited angiogenesis as measured by endothelial cell tube formation on Matrigel. We conclude that invasiveness of human prostate cancer is facilitated by the Rho/Rho-kinase pathway, and exploration of selective Rho-kinase inhibitors for limiting invasive progress of prostate cancer is warranted.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides / pharmacology*
  • Animals
  • Azepines / pharmacology*
  • Cattle
  • Cell Division / drug effects
  • Cells, Cultured
  • Chemotaxis / drug effects
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mice, Transgenic
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Myosin-Light-Chain Phosphatase
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Metastasis / prevention & control
  • Neovascularization, Physiologic / drug effects
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / physiopathology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Pyridines / pharmacology*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • rho-Associated Kinases


  • Amides
  • Azepines
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Pyridines
  • ML 9
  • Y 27632
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • Myosin-Light-Chain Kinase
  • Phosphoprotein Phosphatases
  • Myosin-Light-Chain Phosphatase