Antitumor effect of vandetanib through EGFR inhibition in head and neck squamous cell carcinoma.
BACKGROUND
The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) have been implicated as therapeutic targets for head and neck squamous cell carcinoma (HNSCC). Vandetanib is a small-molecule tyrosine kinase inhibitor (TKI) with dual specificity for EGFR and VEGFR. Here we characterize the phenotypic and biochemical effects of vandetanib on various HNSCC cell lines.


METHODS
In vitro models were used for studying tumor cell viability, invasion, and signaling as well as in vivo xenograft models.


RESULTS
Treatment with vandetanib reduced viability, invasion, and tumor growth of HNSCC cell lines. Phosphorylation levels of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) were reduced in vandetanib-treated HNSCC cells. Additionally, vandetanib abrogates EGF-induced STAT3 activity and STAT3 target gene expression.


CONCLUSIONS
We demonstrated that vandetanib inhibits the growth of head and neck cancer cell lines. The antitumor effects of vandetanib appear to be exerted via the EGFR inhibitory effect of the compound.
Department of Otolaryngology, School of Medicine, University of Pittsburgh, Pennsylvania, United States.
Jonah D
JD
Klein
Apostolos
A
Christopoulos
Sun M
SM
Ahn
William E
WE
Gooding
Jennifer R
JR
Grandis
Seungwon
S
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D051379:Mice; D058990:Molecular Targeted Therapy; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; D066246:ErbB Receptors; C452423:vandetanib