Aims. We investigated the potential activity of STI571 on signal transduction pathways and its pro-apoptotic effect in osteosarcoma cell lines expressing PDGF and its receptor. Materials and Methods. SCF-receptor and PDGF-receptor expression was evaluated in five human osteosarcoma cell lines by cytofluorimetry and immunohistochemistry. The activation status of these receptors was analysed by immunoprecipitation studies in basal conditions, after stimulation with PDGF, and after stimulation with PDGF and inhibition with STI571, simultaneously. We detected the presence of PDGF in culture media using an Enzyme-Linked ImmunoSorbent Assay. We then performed apoptosis analysis by Terminal desoxy-Uridine Nucleotide Extending Labelling (TUNEL) assay with a scalar concentration of STI571 at 24 and 48 hours. Results. Four cell lines were positive for PDGF-Rβ, one for PDGF-Rα and one slightly positive for both receptors. We observed low levels of c-Kit expression. Detectable levels of PDGF were found in all the supernatants analysed. Immunoprecipitation studies showed a receptor constitutive phosphorilation in basal conditions, amplification of this status with exogenous PDGF and a dose-dependent inhibition by STI571. Discussion. STI571 might interfere with osteosarcoma proliferative signals in vitro by selective inhibition of PDGF-R, suggesting a potential use of this drug in association with traditional antineoplastic agents.
|Number of pages||7|
|Journal||Italian Journal of Pediatrics|
|Publication status||Published - Feb 2005|
- Autocrine loop
- Tyrosine kinase receptor
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health