Activity of Bortezomib in Glioblastoma

Abstract

Background: Chemotherapy is the commonly accepted standard therapy for most types of brain tumor, especially in medulloblastoma, primitive neuroectodermal tumor and astrocytoma. However, no efficient therapy has been established to date for glioblastoma multiforme. The aim of the present study was to analyze the activity of bortezomib in glioblastoma cell lines in comparison with that in a pediatric acute lymphoblastic leukemia cell line. Materials and Methods: Glioblastoma multiforme T98G, glioblastoma-astrocytoma U373M and T-lineage acute lymphoblastic leukemia CCRF-CEM cell lines were used. Proteasome inhibitor, bortezomib and 14 other anticancer drugs were tested using the MTT assay. Results: Compared to the acute lymphoblastic cell line, both glioblastoma cell lines showed relatively good sensitivity to bortezomib, as well as to cisplatin, carboplatin, etoposide and actinomycin-D. The lines showed intermediate sensitivity to thiotepa and daunorubicin, but were highly resistant to first-line drugs used in the therapy of acute lymphoblastic leukemia, such as prednisolone, L-asparaginase, vincristine, doxorubicin and cytarabine. Bortezomib, which is not a substrate for PGP and MRP1, did not show cross resistance to drugs transported by these proteins. Conclusion: Our results support the necessity for further research on the role of bortezomib in the therapy of glioblastoma.