RT Journal Article
SR Electronic
T1 Quantification of the Expression of Multidrug Resistance-related Genes in Human Tumour Cell Lines Grown with Free Doxorubicin or Doxorubicin Encapsulated in Polyisohexylcyanoacrylate Nanospheres
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3781
OP 3788
VO 24
IS 6
A1 ARMELLE LAURAND
A1 AUDREY LAROCHE-CLARY
A1 ANNICK LARRUE
A1 SYLVIE HUET
A1 ÉMILIENNE SOMA
A1 JACQUES BONNET
A1 JACQUES ROBERT
YR 2004
UL http://ar.iiarjournals.org/content/24/6/3781.abstract
AB Doxorubicin (dox) encapsulated in polyisohexylcyanoacrylate nanospheres (PIHCA-dox) can circumvent P-glycoprotein-mediated multidrug resistance (MDR). In order to investigate whether this drug formulation is able to select MDR cells in culture in the same way as free doxorubicin does, two human tumour cell lines, K562 and MCF7, were grown with increasing concentrations of either free dox or PIHCA-dox. For both drug formulations and for each selection level, the cell lines were more resistant to free dox than to PIHCA-dox. The MCF7 sublines selected with PIHCA-dox exhibited a higher level of resistance to both doxorubicin formulations than those selected with free doxorubicin. Different levels of overexpression of several genes involved in drug resistance (MDRl, MRP1, BCRP and TOP2·) occurred in the resistant variants. MDR1 gene overexpression was consistently higher in free dox-selected cells than in PIHCA-dox-selected cells, while this was the reverse for the BCRP gene. Overexpression of the MRP1 and TOP2· genes was also observed in the selected variants. Our results show that several mechanisms may be involved in the acquisition of drug resistance and that drug encapsulation markedly alters or delays these processes. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved