Expression of ABC-1 transporter is elevated in human glioma cells under irradiation and temozolomide treatment.
OBJECTIVE
Chemo-therapeutic treatment of glioma patients has minor success. Little is known about mechanisms of a pronounced resistance of gliomas towards actual therapies, yet. ABC-1 belongs to the group of transporters known to be involved in the export of hydrophobic substances and vascular regulation. This study investigates an effect of both temozolomide (TMZ) treatment and/or irradiation on the expression of the ABC-1 transporter in human U87-MG glioma cells.


METHODS
In parallel experiments U87-MG cells underwent either irradiation (RT), chemo-treatment (CT) using TMZ, and combined chemo/radiation-treatment (CT/RT). After each treatment the cells were incubated either 2 or 24 hours at 37 degrees C and counted before protein analysis using Western-Blot technique.


CONCLUSIONS
An exponential growth of cellular density was observed for both untreated and irradiated cells being, however, about 2-times slower in irradiated compared to untreated cells. In contrast the density increase of chemo-treated cells as well as that of cells, which underwent the combined CT/RT treatment was of linear nature. ABC-1 expression was detected in untreated as well as treated cells. Increasing cell density and all kinds of treatment resulted in a considerably enhanced ABC-1 expression. CT treatment resulted in highly up-regulated ABC-1 expression especially in non-confluent cultures compared to untreated cells. Irradiation had a comparable or even higher inducible effect on the ABC-1 expression rates depending, however, on cell density. The highest expression rates were observed in cultures with high cellular density 2 hours after application of the combined treatment. Strong up-regulation of ABC-1 expression under both irradiation and chemo-treatment might be a clue to multidrug and irradiation cross-resistance mechanisms of malignant glioma cells converting the ABC-1 transporter into an attractive pharmacological target for a clinical breakthrough in the therapy of malignant gliomas.
Trog
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Department of Radiology, Division of Molecular/Experimental Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany.
Moenkemann
H
H
Haertel
N
N
Schüller
H
H
Golubnitschaja
O
O
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D000077204:Temozolomide; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D018528:ATP-Binding Cassette Transporters; D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide