ROCK inhibition as a potential therapeutic target involved in apoptosis in hemangioma

Oncol Rep. 2017 May;37(5):2987-2993. doi: 10.3892/or.2017.5515. Epub 2017 Mar 21.

Abstract

Gene expression was examined in hemangiomas (HA), benign, birthmark-like tumors occurring in infancy, and confirmed in HA-derived endothelial cells (HDEC), for which cell proliferation and apoptosis were also assessed. Protein and mRNA accumulation of Rho-associated protein kinase (ROCK), vascular endothelial growth factor (VEGF), Ki-67 and proliferating cell nuclear antigen was significantly higher in proliferating phase HAs than in involuting phase HAs. In contrast, p53 and caspase-3 exhibited higher levels of accumulation in involuting than proliferating HAs. Cell apoptotic indexes were low in proliferating phase HAs and increased in involuting phase HAs. HDECs were treated with the ROCK inhibitor Y-27632. Y-27632 induced p53 expression and downregulated VEGF expression, significantly inhibited cell proliferation, and induced cell apoptosis in HA cells. The inhibitor effects were confirmed in HAs from HDEC-injected nude mice. These results indicated that ROCK is involved in p53-mediated apoptosis and VEGF expression in HA cells and suggested that such inhibition may be exploited for future HA therapies.

MeSH terms

  • Amides / administration & dosage*
  • Amides / pharmacology
  • Animals
  • Apoptosis
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation / drug effects
  • Hemangioma / drug therapy*
  • Hemangioma / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Proliferating Cell Nuclear Antigen / metabolism
  • Pyridines / administration & dosage*
  • Pyridines / pharmacology
  • Tumor Suppressor Protein p53 / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*
  • rho-Associated Kinases / metabolism*

Substances

  • Amides
  • Proliferating Cell Nuclear Antigen
  • Pyridines
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Y 27632
  • rho-Associated Kinases