title: Anticancer drugs exert differential apoptotic and cytotoxic effects on glioblastoma primary cultures with various EGFR and bcl-2 profiles.
abstract: 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.
authors.affiliation: 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
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pédeboscq
authors.forename: Béatrice
authors.initials: B
authors.lastname: L'Azou
authors.forename: Isabelle
authors.initials: I
authors.lastname: Passagne
authors.forename: Francesca
authors.initials: F
authors.lastname: De Giorgi
authors.forename: François
authors.initials: F
authors.lastname: Ichas
authors.forename: Dominique
authors.initials: D
authors.lastname: Liguoro
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pometan
authors.forename: Jean
authors.initials: J
authors.lastname: Cambar
mesh_terms: 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
chemical_list: 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