BCL-2 family proteins modulate radiosensitivity in human malignant glioma cells.
Radiotherapy is the standard treatment for glioblastoma. Here, we assessed the radiosensitivity of 12 human malignant glioma cell lines in vitro and correlated these data with irradiation-induced cell cycle changes, chemosensitivity profiles and BCL-2 family protein expression. Irradiation at 3 Gy failed to cause major cell cycle perturbations. Radioresistance was associated with collateral sensitivity to the topoisomerase II inhibitors, teniposide and doxorubicin. High levels of BCL-XL and low levels of BAX were independently linked to radioresistance. Ectopic expression of a BAX transgene induced radiosensitization in the LN-18 cell line. Thus, BCL-2 family protein expression modulates radiosensitivity in human glioma cells and targeted alterations in BCL-2 family protein expression are a promising strategy to improve the therapeutic efficacy of radiotherapy for gliomas.
Streffer
Johannes R
JR
Department of Neurology, University of Tübingen, Germany.
Rimner
Andreas
A
Rieger
Johannes
J
Naumann
Ulrike
U
Rodemann
Hans-Peter
HP
Weller
Michael
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D018014:Gene Transfer Techniques; D005910:Glioma; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000528:radiation effects; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein