Anticancer drugs exert differential apoptotic and cytotoxic effects on glioblastoma primary cultures with various EGFR and bcl-2 profiles.
The aim of this study was to determine the apoptotic and cytotoxic effects induced on glioblastoma cells by various anticancer agents that possess different mechanisms of action (alkylating drugs, anti-EGFR (Epidermal Growth Factor receptor), proteasome inhibitor). Primary cell cultures were obtained from patients who underwent surgery for their glioblastoma. The cytotoxic effects of drugs were determined by MTT (dimethylthiazolyl diphenyl tetrazolium bromide) assay and apoptosis was evaluated by measuring mitochondrial potential by flow cytometry. Biological markers (EGFR, bcl-2) were studied by a immunoblotting technique to find out predictive markers of response. We found a large interindividual sensitivity, thus confirming the interest of the primary cultures. New proteasome inhibitor bortezomib had considerable cytotoxic and apoptotic potential in glioblastoma, even at very low concentrations. Moreover, the characterization of patients' cells for EGFR and bcl-2 status could constitute an interest, with the evaluation of other markers, in the study of expected chemotherapy response.
Pédeboscq
Stéphane
S
Laboratoire de Biologie Cellulaire, Travail, Environnement EA 3672, Université Victor Segalen, Bordeaux 2, 146 rue Léo Saignat, 33 076 Bordeaux, France. stephane.pedeboscq@chu-bordeaux.fr
L'Azou
Béatrice
B
Passagne
Isabelle
I
De Giorgi
Francesca
F
Ichas
François
F
Liguoro
Dominique
D
Pometan
Jean-Paul
JP
Cambar
Jean
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D019254:Genes, bcl-2 / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004396:Coloring Agents; D005904:Glial Fibrillary Acidic Protein; D013778:Tetrazolium Salts; D013844:Thiazoles; D066246:ErbB Receptors; C022616:thiazolyl blue