Doxorubicin-resistant, MRP1-expressing U-1285 cells are sensitive to idarubicin.
A doxorubicin-resistant subline (U-1285dox(900)) was derived from the human small cell lung carcinoma cell line U-1285. U-1285dox(900) was exposed to a wide range of anticancer agents to determine its resistance profile. In contrast to U-1285 cells, the resistant subline U-1285dox(900) expressed elevated MRP1 mRNA detected by reversed transcriptase-polymerase chain reaction (RT-PCR) and MRP1 protein analyzed with Western blot. Neither MDR1 mRNA nor P-glycoprotein could be detected in the parental cell line or resistant subline. U-1285dox(900) exhibited high resistance to doxorubicin, epirubicin, daunorubicin, and vincristine, an intermediate resistance to mitoxantrone, and a low resistance to etoposide. A collateral sensitivity to cytosine arabinoside, chlorodeoxyadenosine, and melphalan was observed. The resistance could be reversed by buthionine-sulphoximine and verapamil for all tested drugs. Compared with daunorubicin, resistance to idarubicin was very low, 14-fold and 2.6-fold, respectively. This was associated with a higher accumulation due to a slower transport of idarubicin out of U-1285dox(900) cells.
Jönsson-Videsäter
Kerstin
K
Department of Medicine, Huddinge University Hospital, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Andersson
Göran
G
Bergh
Jonas
J
Paul
Christer
C
D019540:Area Under Curve; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D004317:Doxorubicin; D015255:Idarubicin