Artikel
In vitro study of imatinib and carboplatin in HNSCC
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Veröffentlicht: | 6. Juli 2010 |
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Gliederung
Text
Protein-tyrosins-kinases (PTK) are important targets for chemical agents that inhibit their activities. In HNSCC only the EGFR-PTK inhibitor gefitinib (Iressa®) has been studied extensively. The PTK inhibitor Imatinib (Glivec®, also known as STI571, Novartis, Basel, Switzerland) belongs to the 2-phenylaminopyrimidine class, which was developed for its selectivity against BCR-ABL in patients with chronic myeloid leukemia. But it is also an inhibitor of platelet-derived growth factor receptor (PDGFR) PTK. The purpose of this study was to evaluate the effects of imatinib (STI 571) in HNSCC cell culture. The expression of VEGF/PDGF-R and apoptosis was analysed not only after incubation with imatinib but also after combination of imatinib with carboplatin. To our knowledge, this is the first report of a chemotherapeutic study treating HNSCC with imatinib and carboplatin.
UM-SCC cell lines were incubated with various combinations of carboplatin and/or imatinib over a period of 48 hours to 10 days. After a certain incubation time VEGF and PDGF-R expression was analyzed using ELISA, immunohistochemistry and quantitative PCR.
The UM-SCC cell line 22B showed a significant reduction of VEGF expression. Another significant reduction in PDGF-R expression was observed in the cell line 22B. The two other examined cell lines showed only a trend towards a reduced VEGF and PDGF-R expression. But we could not achieve a difference in apoptosis of the cell cultures.
Thus imatinib seems to influence, most likely over the PDGF/PDGF-R pathway, VEGF expression. In consequence imatinib might offer a new therapeutic regimen in HNSCC, but further in-vitro studies are necessary.