CHEMOTHERAPY OF HUMAN-MALIGNANT GLIOMA - PREVENTION OF EFFICACY BY DEXAMETHASONE

Steroids are commonly administered for the control of edema, mass effe ct, and side effects from therapy to patients with malignant glioma wh o are receiving radiotherapy and chemotherapy. Here, we report that th erapeutic concentrations of dexamethasone (DEX) attenuate cytotoxicity and growth inhibition of human malignant glioma cells induced by expo sure to several chemotherapeutics, including ACNU, VM-26, vincristine, cytarabine, methotrexate, and adriamycin. DEX-mediated cytoprotection is not linked to DEX effects on glioma cell proliferation. However, t he cytoprotective effects of DEX appeared to be more prominent in cell lines with wild-type p53 status (n = 2) than in p53 mutant cell lines (n = 3). Further, DEX-mediated rescue from chemotherapy does not dire ctly involve Bcl-2 family proteins since DEX failed to change the expr ession of Bcl-2 or Bax proteins and since bcl-2 gene transfer-mediated cytoprotection was not redundant with the effects of DEX. DEX thus ap pears to control a common, bcl-2-independent death pathway in glioma c ells that is not limited to specific drug actions. Chemotherapy is usu ally given as an elective, adjuvant treatment to glioma patients in st able condition who can tolerate steroid withdrawal. To maximize therap eutic efficacy, steroids should be withdrawn from glioma patients prio r to chemotherapy.