Characterization of newly established adriamycin resistant human leukemic cell lines (KY-ADR1 and KY-ADR2).
New adriamycin (ADR) resistant human leukemic cell lines (KY-ADR1 and KY-ADR2) have been established. KY-ADR1 was selected from a cytosine arabinoside (Ara C) resistant cell line by gradually increasing the concentration of ADR and KY-ADR2 from the parental cell line, KY-821, by the same method. The IC50s of both cell lines were 4.3 x 10(-5) and 3.6 x 10(-5) M ADR, respectively. Both lines revealed a similar cross resistance to various anticancer drugs, but KY-ADR1 was resistant to Ara C, whereas KY-ADR2 was sensitive. MDR1 gene was over-expressed and P-glycoprotein was expressed on the cytoplasmic membrane in both lines. Neither verapamil nor cyclosporin A could completely reverse ADR resistance. In addition, no significant changes in topoisomerase II and glutathione-s-transferase levels were detected. These findings indicate that ADR resistance in both cell lines is mainly mediated by P-glycoprotein and some other mechanism may be present. Interestingly, growth of both cell lines was stimulated by natural IL-1 and not affected by TNF alpha and IFN gamma, whereas growth of parental KY-821 was inhibited by these factors. These cell lines will provide new biological aspects on drug resistant leukemic cells.
Fukuda
T
T
Second Department of Pathology, Niigata University School of Medicine, Japan.
Kakihara
T
T
Kamishima
T
T
Ohnishi
Y
Y
Naito
M
M
Kishi
K
K
Shibata
A
A
Tsuruo
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007700:Kinetics; D007938:Leukemia; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D006133:Growth Substances; D007375:Interleukin-1; D003561:Cytarabine; D004317:Doxorubicin; D013936:Thymidine