Effect of STI-571 (imatinib mesylate) in combination with retinoic acid and gamma-irradiation on viability of neuroblastoma cells.
Neuroblastoma (NB) expresses the tyrosine kinase receptors c-Kit, PDGFR-alpha and -beta-targets for STI-571. We investigated a possible combination therapy of STI-571 with retinoic acid (RA) and gamma-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 microM STI-571 for 72h, two cell lines responding already to 10 microM. Cell lines responded irrespective of their mRNA status or cell surface expression of c-Kit, PDGFR-alpha and -beta. 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 gamma-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 gamma-irradiation therapy.
Rössler
Jochen
J
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Hospital of Freiburg, Germany. jochen.roessler@uniklinik-freiburg.de
Zambrzycka
Izabella
I
Lagodny
Jeanette
J
Kontny
Udo
U
Niemeyer
Charlotte Marie
CM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001549:Benzamides; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005720:Gamma Rays / Q000627:therapeutic use*; D006801:Humans; D000068877:Imatinib Mesylate; D009447:Neuroblastoma / Q000473:pathology* / Q000628:therapy*; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D014212:Tretinoin / Q000008:administration & dosage*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014212:Tretinoin; D000068877:Imatinib Mesylate