Abstract
Neuroblastoma (NB) expresses the tyrosine kinase receptors c-Kit, PDGFR-α and -β—targets for STI-571.We investigated a possible combination therapy of STI-571 with retinoic acid (RA) and γ-irradiation on NB cell viability in vitro. Expression of tyrosine kinase receptors and their ligands was examined in 6 NB cell lines by RT-PCR and FACS. The effect on cell viability was determined by MTT assay. Cell viability of all 6 NB cell lines was significantly inhibited after treatment with 20 μM STI-571 for 72 h, two cell lines responding already to 10 μM. Cell lines responded irrespective of their mRNA status or cell surface expression of c-Kit, PDGFR-α and -β. Co-incubation with 9- cis RA sensitized cells to the inhibitory effects of STI-571. However, pre-treatment with 9- cis RA resulted in resistance of NB cell lines to STI-571 and γ-irradiation. Treatment of NB with STI-571 in combination with 9- cis RA might be a therapeutic strategy for patients in consolidation therapy who have completed γ-irradiation therapy.
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