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Vandetanib Inhibits Growth of Adenoid Cystic Carcinoma in an Orthotopic Nude Mouse Model
- Source :
- Clinical Cancer Research. 14:5081-5089
- Publication Year :
- 2008
- Publisher :
- American Association for Cancer Research (AACR), 2008.
-
Abstract
- Purpose: Adenoid cystic carcinoma (ACC) can often be controlled with surgery and postoperative adjuvant radiotherapy but is also characterized by late local recurrence and distant metastasis. No effective systemic therapeutic agents have been found to alter the natural history of ACC. Therefore, new therapeutic approaches are needed. In this study, we evaluated whether vandetanib (Zactima), a potent inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinases, had antitumor efficacy in vitro and in an orthotopic nude mouse model of human ACC.Experimental Design: The in vitro effects of vandetanib were assessed in three ACC cell lines on cell growth, apoptosis, and VEGFR-2 and EGFR phosphorylation levels. The in vivo antitumor activity of vandetanib was examined in nude mice bearing parotid gland ACC tumors. The mice were treated for 4 weeks with vandetanib (50 mg/kg/d) or placebo (control). Tumors were resected at necropsy, and immunohistochemical and immunofluorescence staining were done.Results: In vitro, vandetanib caused dose-dependent inhibition of VEGFR-2 and EGFR phosphorylation in ACC cells. Vandetanib also inhibited the cell proliferation and induced their dose-dependent apoptosis. In vivo, mice in the vandetanib group had tumor volumes significantly lower than those in the control group (P < 0.01). In addition, immunohistochemical staining showed a decrease in microvessel density and an increase in apoptosis of both tumor cells and endothelial cells within the tumor xenografts.Conclusion: These results suggest that vandetanib inhibits the growth of ACC in vitro and in vivo, making it a promising novel agent for the treatment of ACC.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
medicine.drug_class
Blotting, Western
Fluorescent Antibody Technique
Mice, Nude
Antineoplastic Agents
Apoptosis
Biology
Vandetanib
Tyrosine-kinase inhibitor
Mice
chemistry.chemical_compound
Nude mouse
Piperidines
In vivo
Cell Line, Tumor
In Situ Nick-End Labeling
medicine
Animals
Humans
Epidermal growth factor receptor
Phosphorylation
Cell Proliferation
Cell growth
biology.organism_classification
Carcinoma, Adenoid Cystic
Immunohistochemistry
Vascular Endothelial Growth Factor Receptor-2
Xenograft Model Antitumor Assays
Parotid Neoplasms
ErbB Receptors
Vascular endothelial growth factor
Oncology
chemistry
Quinazolines
Cancer research
biology.protein
Tyrosine kinase
medicine.drug
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....7e275c796af16c049bdceeed1f246007