NADPH/quinone oxidoreductase is a priority target of glioblastoma chemotherapy

We attempted to determine a target of chemotherapy specific to glioblastoma cells to ensure a favorable response to anticancer drugs, through comparis on in biologic nature related to drug resistance with other types of cancer cells. Using 13 human cancer cell lines including 3 glioblastoma lines, ge ne expression analysis and biochemical quantitative assay were performed fo r a total of 12 properties, which have been linked to drug action. Although most of genes related to drug resistance, such as MDR1, MRP, MGMT and GST pi, were overexpressed in T98G, U-373MG, and U-251MG glioblastoma cells, To po I (topoisomerase I) expression was relatively low and alpha- and beta-TU B (tubulin) expression was comparable to other types of 10 cell lines. The glioblastoma cell lines also showed an increased expression of NADPH/quinon e oxidoreductase gene (NQO1), but the respective enzyme NQO activated MMC. Among the drugs targeting such properties, MMC was more active than Topo I inhibitors and docetaxel (TXT) due to the lack of other sensitivity (resist ance) determinants. Differing from MMC, MGMT was shown to participate in th e resistance of Topo I inhibitors (CPT-11, SN38 and DX-8951f), while GST pi and MDR1 were involved in docetaxel (TXT) resistance. MMC was also more ac tive than ACNU and CDDP in the three glioblastoma cells. NQO may be a prior ity target of glioblastoma chemotherapy suitable for biochemical nature of the cells, and expression analysis of NQO1, alpha-TUB, beta-TUB, MGMT, MDR1 and GST pi may help to seek a truly active drug against glioblastomas.