TY - JOUR 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 SP - 3781 LP - 3788 VL - 24 IS - 6 AU - ARMELLE LAURAND AU - AUDREY LAROCHE-CLARY AU - ANNICK LARRUE AU - SYLVIE HUET AU - ÉMILIENNE SOMA AU - JACQUES BONNET AU - JACQUES ROBERT Y1 - 2004/11/01 UR - http://ar.iiarjournals.org/content/24/6/3781.abstract N2 - 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 ER -