In vitro modulation of CD95 expression on a human glioblastoma cell line by various chemotherapeutic drugs

The CD95-mediated pathway may be relevant in regulating drug sensitivity of tumor cells because this system, consisting of a membrane-bound isoform and its natural ligand (CD95L), might be modulated in response to drug treatment. In this study, using a CD95+ human glioblastoma cell line, we investigated the in vitro effects of various chemotherapeutic drugs on CD95 expression. Alterations in the susceptibility of this cell line to Fas-dependent apoptosis following drug exposure were also evaluated. Our results show that in vitro treatment of GBM cell with mitoxantrone, topotecan and CPT-83 induced an up-regulation of CD95 expression, whereas other drugs such as cisplatin and taxol did not. In the case of topotecan and CPT-83, the drug-induced up-regulation of CD95 was concomitant to an increased susceptibility of GBM cells to Fas-dependent apoptosis. The observed up-regulation of CD95 expression and Fas-dependent apoptosis might have important therapeutic implications because cells could be sensitive to specific DNA-damaging agents through activation of the CD95 pathway. The profile of expression of CD95 might be a useful additional tool in the choice of the optimal chemotherapeutic regimen in glioblastoma.