R. Testi et al., EVALUATION OF RESISTANCE INDEX OF SEVERAL ANTICANCER AGENTS ON PARENTAL AND RESISTANT P-388 CELL-LINES, Leukemia research, 19(4), 1995, pp. 257-261
Multidrug resistance is frequently detected in haematological malignan
cies and in acute leukaemias with a poor prognosis. In the last few ye
ars, several reports seem to suggest that the new anthracycline deriva
tive idarubicin and the anthraquinone mitoxantrone have some advantage
s in the management of untreated or relapsed acute leukaemias compared
with older anthracyclines. This could be due to a different interacti
on of these drugs with multidrug resistance. To evaluate this possibil
ity, we compared the activity of doxorubicin (DOXO), epirubicin (EPI),
idarubicin (IDA) and mitoxantrone (MITO) on a murine, multidrug resis
tant, leukaemic cell line (P-388/Dx) cultured in vitro. ID50 of IDA an
d MITO was in the ng range whereas that of DOXO and EPI was in the mu
g range. Moreover, IDA has a resistance index of 50 whereas DOXO has o
ne of 250. Verapamil is able to almost completely abolish the resistan
ce to IDA. Efflux experiments confirm that verapamil increases IDA int
racellular concentration. IDA and MITO appear to be less involved in m
ultidrug resistance than older anthracyclines.