Growth factor receptors signaling in glioblastoma cells: therapeutic implications.
In this study, we investigated the protein expression of platelet-derived growth factor receptor (PDGFR), insulin like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK1/2) in five primary glioblastoma (GB), with a view to their possible use as therapeutic targets. Our results demonstrated that appreciable levels of these proteins could be detected in the analysed GB cell lines, except for a low level of PDGFR and ERK1/2 expression in one GB cell line. The small molecule inhibitors towards IGF-1R, PDGFR, PI3-K and ERK1/2 respectively, have only modest or no anti-tumour activity on GB cells and therefore their combination with other therapy modalities was analysed. The interaction between small inhibitors and radiation was mostly additive or sub-additive; synergistic interaction was found in five of forty analysed combinations. Our results showed that GB cells are in general resistant to treatment and illustrate the difficulties in predicting the treatment response in malignant gliomas.
Carapancea
Mia
M
Department of Oncology-Pathology, Cancer Center Karolinska and Radiumhemmet Karolinska Institute/University Hospital, R8:00, 171 76, Stockholm, Sweden.
Alexandru
Oana
O
Fetea
Ani S
AS
Dragutescu
Laura
L
Castro
Juan
J
Georgescu
Ada
A
Popa-Wagner
A
A
Bäcklund
Magnus L
ML
Lewensohn
Rolf
R
Dricu
Anica
A
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D017978:Receptors, Growth Factor / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D000970:Antineoplastic Agents; D017978:Receptors, Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D017479:Receptors, Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3