Antitumor activity of enzastaurin as radiation sensitizer in head and neck squamous cell carcinoma

Head Neck. 2011 Aug;33(8):1106-14. doi: 10.1002/hed.21578. Epub 2010 Oct 21.

Abstract

Background: The antitumor effect of enzastaurin, a specific protein kinase C beta (PKC-β) inhibitor, was tested on head and neck squamous cell carcinoma (HNSCC) cell lines, as well as HNSCC xenograft model.

Methods: HNSCC cell lines and xenograft were treated with enzastaurin alone or in combination with radiation to evaluate its antitumor effect. Annexin V-FITC staining and Western blot were done to analyze enzastaurin-induced changes in apoptosis and the PIK3/AKTAKT signal transduction pathway.

Results: Enzastaurin showed strong antitumor activity either alone or in combination with radiation both in HNSCC cell lines and in xenograft, with a corresponding reduction in the expression of key radioresponsive proteins.

Conclusion: Enzastaurin can inhibit tumor growth and improve the efficacy of radiation for HNSCC both in vitro and in vivo. This suggests that enzastaurin may represent a better strategy for the treatment of HNSCC patients, either as a monotherapy or as a radiosensitizer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / radiation effects
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Indoles / pharmacology*
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / prevention & control*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C beta
  • Radiation-Sensitizing Agents / pharmacology*
  • Random Allocation
  • Sensitivity and Specificity
  • Squamous Cell Carcinoma of Head and Neck
  • Xenograft Model Antitumor Assays

Substances

  • Indoles
  • Radiation-Sensitizing Agents
  • Protein Kinase C
  • Protein Kinase C beta
  • enzastaurin