Fiche publication
Date publication
mars 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHASTAGNER Pascal
,
Dr PINEL Sophie
Tous les auteurs :
Labussiere M, Pinel S, Vandamme M, Plenat F, Chastagner P
Lien Pubmed
Résumé
PURPOSE: To investigate the influence of the bortezomib (BTZ) on malignant glioma radiosensitivity in two xenograft models. METHODS AND MATERIALS: For TCG3 and U87 models, we evaluated the antitumor activity of BTZ, radiotherapy, and BTZ plus radiothearapy according to two therapeutic schedules: a "nonfractionated" schedule corresponding to a single dose of treatment per week, and a "fractionated" schedule corresponding to the same weekly dose divided into 5 fractions. Treatments influence on proliferation and apoptosis indexes, cell cycle distribution, and nuclear factor-kappaB pathway were explored. RESULTS: The radiosensitizing properties of BTZ observed with the nonfractionated schedule were lost with the fractionated schedule. Bortezomib-mediated radiosensitization was associated with an increased apoptosis response and major changes in cell proliferation, but the nuclear factor-kappaB pathway was not involved. Most of the cellular effects induced by BTZ when tumors received a single irradiation were cancelled out if radiotherapy was fractionated. CONCLUSION: The influence of BTZ on glioma radiosensitivity seems to depend on the treatment fractionation schedule, emphasizing the need to clarify the mechanisms underlying BTZ's radiosensitizing effects before further clinical trials are initiated.
Référence
Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):892-900
