J Korean Assoc Maxillofac Plast Reconstr Surg.  2006 May;28(3):193-201.

Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases in oral squamous cell carcinoma

Affiliations
  • 1Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University, 120 Gangneung Daehangno, Gangneung City Gangwon Province, 210-702, Korea. ywpark@kangnung.ac.kr
  • 2Department of Oral Pathology, College of Dentistry, Kangnung National University, Kangnung National University, 120 Gangneung Daehangno, Gangneung City Gangwon Province, 210-702, Korea.

Abstract

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

Keyword

Oral squamous cell carcinoma; Epidermal growth factor receptor; Vascular endothelial growth factor receptor-2

MeSH Terms

Apoptosis
Carcinoma, Squamous Cell*
Cell Line
Epidermal Growth Factor*
Head
Humans
Neoplasm Metastasis
Phosphorylation
Phosphotransferases
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor*
Survival Rate
Tyrosine
Vascular Endothelial Growth Factor A*
Vascular Endothelial Growth Factor Receptor-2
Epidermal Growth Factor
Phosphotransferases
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor
Tyrosine
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
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