DAUNORUBICIN AND DOXORUBICIN BUT NOT BCNU HAVE DELETERIOUS EFFECTS ONORGANOTYPIC MULTICELLULAR SPHEROIDS OF GLIOMAS

In the present study organotypic multicellular spheroids (OMS) were us ed to study the effects of chemotherapeutic agents on malignant glioma s. Compared with the frequently used cell line models, OMS have severa l advantages with respect to the preservation of the cellular heteroge neity and the structure of the original tumour. OMS prepared from seve n glioma specimens were treated with 1,3-bis(2-chloroethyl)-1-nitrosou rea (BCNU), daunorubicin or doxorubicin. After exposure to these drugs , the histology and cell proliferation of the OMS were analysed by imm unohistochemistry and image analysis. Furthermore, the expression of P -glycoprotein (P-gp) and multidrug resistance-related protein (MRP), w hich both can contribute to resistance to daunorubicin and doxorubicin , were immunohistochemically investigated. We found that OMS from glio mas are sensitive for daunorubicin and doxorubicin but not for BCNU in terms of tissue destruction and decrease in cell proliferation. In ad dition, all gliomas were P-gp and MRP negative, which is in accordance with the sensitivity for daunorubicin and doxorubicin. Considering th e potential use of several new alternative drug delivery methods, such as intratumoural implantation of drug-impregnated polymers or liposom al encapsulation of cytostatic drugs, daunorubicin and doxorubicin mig ht be effective in the treatment of malignant gliomas.