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Recovery of drug sensitivity by MS‐209, a new multidrug resistance‐reversing agent, on acute myelogenous leukaemic blasts and K562 cells resistant to adriamycin cell line
Author(s) -
Wang Y. H.,
Motoji T.,
Motomura S.,
Shiozaki H.,
Tsuruo T.,
Mizoguchi H.
Publication year - 1997
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1997.tb00946.x
Subject(s) - daunorubicin , k562 cells , multiple drug resistance , medicine , leukemia , pharmacology , rhodamine 123 , drug resistance , intracellular , cell culture , precursor cell , cancer research , immunology , cell , chemistry , biology , biochemistry , genetics , microbiology and biotechnology
The efficacy of MS‐209, a quinoline derivative synthesized as a new multidrug resistance (MDR)‐reversing agent, was studied on blast cells from 33 acute myelogenous leukaemia (AML) patients and on the human myelogenous leukaemia K562 cell line resistant to adriamycin (K562/ADM). By the addition of MS‐209, the intracellular daunorubicin (DNR) contents which had been found to be low in P‐gp‐positive AML blasts and in K562/ADM were significantly enhanced to the level of P‐gp‐negative blasts and that of sensitive K562. The intracellular rhodamine (Rh123) contents also increased in P‐gp‐positive blasts and K562/ADM cells with MS‐209. A leukaemic blast colony assay also demonstrated the effect of MS‐209, i.e. a high D 10 value for DNR of P‐gp‐positive blasts was reduced to the D 10 level similar to that observed in P‐gp‐negative blasts by the addition of MS‐209. The greater DNR sensitivity reversing effect of MS‐209 was observed in blasts with higher P‐gp positivity. These findings suggest the potential usefulness of MS‐209 in overcoming MDR in AML patients, especially those with high P‐gp expression. This study clarified the relationship between the clinical outcome of the patients and the P‐gp positivity, intracellular DNR content and DNR drug sensitivity of leukaemic progenitors.