Influence of chemosensitizers on resistance mechanisms in daunorubicin-resistant Ehrlich ascites tumour cells.

Aim: To determine whether treatment with chemosensitizers influences the development of the drug-resistant phenotype.

Methods: Three sublines were developed from the sensitive Ehrlich ascites tumour cell line (EHR2) and six sublines from the EHR2/DNR cell line positive for P-glycoprotein (PGP) by treatment with daunorubicin (DNR), a combination of DNR and verapamil (VER), or a combination of DNR and cyclosporin A (CsA). A clonogenic assay was used to determine resistance, the expression of PGP, the multidrug resistance associated protein ( Mrp1) and topoisomerase IIalpha and beta were measured by Western blotting, and reverse transcriptase-polymerase chain reaction was used for determination of mdr1a and b, and Mrp1 mRNA.