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Summary: A doxorubicin-resistant subline (U-1285dox900) was derived from the human small cell lung carcinoma cell line U-1285. U-1285dox900 was exposed to a wide range of anticancer agents to determine its resistance profile. In contrast to U-1285 cells, the resistant subline U-1285dox900 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-1285dox900 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-1285dox900 cells.

(C) 2003 Lippincott Williams & Wilkins, Inc.