Head and neck squamous cell carcinoma (
HNSCC) is an aggressive epithelial
malignancy. The development of new treatment modalities in order to improve long-term survival of patients with
HNSCC is imperative. Numerous studies have demonstrated that
carcinogenesis and
tumor cell dissemination is influenced by the tumor microenvironment. The
protein-kinase-receptors (PTKs) are essential elements of the intracellular signal transduction pathway and regulate cell growth, development and apoptosis. Cell proliferation, migration, induction of
tumor vascularization and
carcinogenesis, invasion is regulated by a variety of angiogenic factors, such as PDGF (
platelet-derived growth factor),
VEGF (
vascular endothelial growth factor) and their respective
tyrosine kinase receptors (PDGF-R and
VEGF-R). They present promising targets for anti-
cancer therapy through abrogation of impaired signaling pathways. Indeed,
imatinib, a small molecule drug targeting these
protein kinases, has antiproliferative effects in several
cancer types. The purpose of this study was to investigate the potential synergism of
imatinib and
carboplatin on the expression of PDGF, PDGF-R α/ß and
VEGF in different
HNSCC cell lines. Several tumor cell lines were subjected to increasing concentrations of
carboplatin (3 and 7.5 µmol/l) and
imatinib (18 and 30 µmol/l) and ELISA, immunohistochemical methods and RQ-PRC after 48, 72, 120 and 240 h were used to assess their expression levels. While PDGF-Rα/ß expression was unimpaired at lower
imatinib concentrations (18 µmol/l), PDGF-Rα/ß expression was suppressed at 30 µmol/l, and suppression was enhanced by the presence of
carboplatin. By RQ-PCR, a significant reduction of PDGF-Rα/ß expression was detected (p<0.5). We observed explicit significant reduction in
VEGF levels with increasing concentrations of
imatinib and with the combination of the two chemotherapeutic drugs (p<0.5). We report for the first time evidence of synergism of
imatinib and
carboplatin in suppressing
VEGF, PDGF and PDGF-Rα/ß expression in
HNSCC.