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

Abstract

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. 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. 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. 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.