Evaluation of antitumor activity of gefitinib in pediatric glioblastoma and neuroblastoma cells.
BACKGROUND
This work was undertaken to investigate the efficacy of gefitinib, an EGFR tyrosine kinase inhibitor, in tumor cell lines of the CNS by studying cell proliferation and phosphorylation of the tyrosine kinase domain of


METHODS
The study included neuroblastoma (SHSY5Y) and glioblastoma (A172) cell lines. The MTT cell proliferation assay was performed in order to quantify the cytotoxic effect of gefitinib in A172 and SH-SY5Y cells, whilst ELISA assay was used to assess the effect on the phosphorylation of tyrosine residue 1068 of EGFR.


RESULTS
As the concentration of gefitinib increased, MTT conversion into formazan was observed to progressively decrease, confirming the cytotoxic activity of gefitinib. In the ELISA assay for both cell lines investigated, as the dose of gefitinib increased, a gradual decrease in EGFR tyrosine phosphorylation was detected.


CONCLUSIONS
The findings of the current study could form the basis of research regarding the use of novel inhibitors in the treatment of solid tumors in pediatric patients and a shift to targeted therapy with higher efficacy and fewer side effects.
Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece.
K
K
Hatziagapiou
M
M
Braoudaki
M
M
Karpusas
F
F
Tzortzatou-Stathopoulou
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D000077156:Gefitinib; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D000077156:Gefitinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases