Bax expressed from a herpes viral vector enhances the efficacy of N,N'-bis(2-hydroxyethyl)-N-nitrosourea treatment in a rat glioma model.
N,N'-bis(2-hydroxyethyl)-N-nitrosourea (BCNU) is a commonly used agent for treatment of malignant gliomas. The mechanisms of cell death and the role of Bcl-2 and Bax in a BCNU-treated rat glioma cell line were investigated. Our results indicate that apoptosis occurs only at a high concentration of BCNU with elevated levels of Bax and a reversed ratio of Bax/Bcl-2. Overexpression of Bax delivered by a herpes simplex viral vector in combination with BCNU chemotherapy enhanced the efficacy of BCNU in a rat glioma model. These findings suggest that conventional treatment with BCNU may be combined with gene therapy that delivers a bax gene into the glioma cells to achieve a high level of Bax, facilitating BCNU-induced cytotoxicity.
Lee
A
A
Department of Surgery, University of British Columbia, Vancouver, Canada.
DeJong
G
G
Guo
J
J
Bu
X
X
Jia
W W
WW
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000628:therapy*; D002330:Carmustine / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000188:drug therapy / Q000628:therapy*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D018139:Simplexvirus / Q000235:genetics*; D051028:bcl-2-Associated X Protein
D018906:Antineoplastic Agents, Alkylating; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002330:Carmustine