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

Abstract

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.

• Authors: Kerstin Jönsson-Videsäter, Göran Andersson, Jonas Bergh, Christer Paul
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 25 Issue 3 Pg. 331-9 (Jun 2003) ISSN: 0163-4356 [Print] United States
• PMID: 12766562 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Doxorubicin
• Idarubicin

Topics

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