Doxorubicin-resistant, MRP1-expressing U-1285 cells are sensitive to idarubicin

Ther Drug Monit. 2003 Jun;25(3):331-9. doi: 10.1097/00007691-200306000-00014.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm / physiology*
  • HL-60 Cells
  • Humans
  • Idarubicin / pharmacology*
  • RNA, Messenger / biosynthesis


  • RNA, Messenger
  • Doxorubicin
  • Idarubicin