期刊
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
卷 79, 期 3, 页码 892-900出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ijrobp.2010.09.051
关键词
Bortezomib; Radiosensitization; Malignant glioma; Treatment fractionation; Cellular effects
资金
- French Ligue Contre le Cancer, Comites Lorrains and Association pour la Recherche sur le Cancer
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-kappa B 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-kappa B 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. (C) 2011 Elsevier Inc.
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