Possible roles of an adult T-cell leukemia (ATL)-derived factor/thioredoxin in the drug resistance of ATL to adriamycin.
Chemotherapy for adult T-cell leukemia (ATL) has been reported to fail to induce complete remission because of drug resistance in most patients. We have examined the expression of an ATL-derived factor (ADF)/thioredoxin in relation to resistance to adriamycin (ADM) in various T-cell leukemia cell lines including ATL cell lines. Immunoblot analysis demonstrated that ATL cell lines expressed ADF/thioredoxin at levels 2.8 to 12 times those of other T-cell acute lymphocytic leukemia (T-ALL) cell lines, and that ATL cell lines were 2 to 15 times more resistant to ADM than other T-ALL cell lines. Therefore, we established ADM-resistant cell lines from three different ATL cell lines, and examined the correlation between ADM resistance and expression of ADF/thioredoxin. ADM-resistant ATL cell lines were also found to be resistant to other drugs such as cisplatin and etoposide, and they expressed ADF/thioredoxin at levels 5 to 10 times those of parent ATL cell lines. Diamide and sodium selenite, which have been reported to inhibit ADF/thioredoxin, restored the sensitivity to ADM in ATL and ADM-resistant ATL cell lines. The MDR-1 gene product, a membrane P-glycoprotein (Pgp), was not expressed on ATL cell lines or ADM-resistant ATL cell lines. Topoisomerase II and glutathione peroxidase activities in T-cell leukemia cell lines were not correlated with ADM resistance. These results suggest that ADF/thioredoxin may play an important role in the drug resistance of ATL cells to ADM.
Wang
J
J
The Third Department of Internal Medicine, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
Kobayashi
M
M
Sakurada
K
K
Imamura
M
M
Moriuchi
T
T
Hosokawa
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D016207:Cytokines / Q000502:physiology*; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D003958:Diamide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005979:Glutathione Peroxidase / Q000032:analysis; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology*; D018038:Sodium Selenite / Q000494:pharmacology; D013879:Thioredoxins / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016207:Cytokines; D009363:Neoplasm Proteins; C055533:adult T cell leukemia-derived factor; D003958:Diamide; D013879:Thioredoxins; D004317:Doxorubicin; D005979:Glutathione Peroxidase; D004250:DNA Topoisomerases, Type II; D018038:Sodium Selenite