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


CONCLUSIONS
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.
Department of Otolaryngology/Head & Neck Surgery, CB # 7295 LCCC, Chapel Hill, NC 27599, USA. xyyin@med.unc.edu
Xiaoying
X
Yin
D Neil
DN
Hayes
Carol G
CG
Shores
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000517:prevention & control*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D064546:Protein Kinase C beta; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
D007211:Indoles; D011838:Radiation-Sensitizing Agents; D011493:Protein Kinase C; D064546:Protein Kinase C beta; C504878:enzastaurin