Cisplatin resistant glioblastoma cells may have increased concentration of urokinase plasminogen activator and plasminogen activator inhibitor type 1.
Gliomas are the most common form of intrinsic primary brain tumors, that extensively invade the surrounding normal brain tissue. The failure of chemotherapy treatment of these tumors is chiefly attributed to drug-resistance. From human glioblastoma we developed two cell sublines resistant to cisplatin due to acute (AT cells) or continuous (CT cells) treatment with clinically relevant doses of cisplatin. We examined their sensitivity to different cytostatics by colorimetric MTT assay. The concentrations of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) were determined by the ELISA assay. The results reveal that both AT and CT cells became resistant to cisplatin and vincristine; AT cells became resistant also to etoposide. Both AT and CT cells did not significantly change their sensitivity to doxorubicin, 5-fluorouracil and chlorambucil. Concentrations of uPA and PAI-1 were increased in CT cells, with no change in AT cells. In the conditioned medium of both, AT and CT cells, the level of uPA were increased. No differences in concentrations of PAI-1 in the conditioned medium of these cells were found. Thus, our results show that drug-resistance of glioblastoma cells may be accompanied with the increased levels of markers for tumor invasion.
Department of Molecular Genetics, Ruder Bosković Institute, Zagreb, Croatia. osmak@rudjer.irb.hr
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Vrhovec
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D000970:Antineoplastic Agents / Q000633:toxicity*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D005047:Etoposide / Q000633:toxicity; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007700:Kinetics; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D014750:Vincristine / Q000633:toxicity
D000970:Antineoplastic Agents; D017395:Plasminogen Activator Inhibitor 1; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D014568:Urokinase-Type Plasminogen Activator; D002945:Cisplatin