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 o f Bcl-2 and Bar in a BCNU-treated rat glioma cell line were investigated. O ur results indicate that apoptosis occurs only at a high concentration of B CNU with elevated levels of Bar and a reversed ratio of Bax/Bcl-2. Overexpr ession of Bar delivered by a herpes simplex viral vector in combination wit h BCNU chemotherapy enhanced the efficacy of BCNU in a rat glioma model. Th ese findings suggest that conventional treatment with BCNU may be combined with gene therapy that delivers a bar gene into the glioma cells to achieve a high level of Bar, facilitating BCNU-induced cytotoxicity.