Induced multidrug-resistance in murine sarcoma 180 cells grown in vitro and in vivo and associated changes in expression of multidrug-resistance DNA-sequences and membrane glycoproteins

Abstract

The aim of this investigation was to analyze the resistance to doxorubicin and daunorubicin of murine sarcoma 180 cells grown in vitro (monolayer) and in vivo (ascites form). The colchicine-resistant CHO cells were used as controls. A multidrug-resistant phenotype was found in all investigated cell lines. Multidrug resistant cells grown in tissue culture or as ascites tumor cells needed more time to accumulate rhodamine 123 than their sensitive parental cells. In order to evaluate whether the resistant cells show alterations in the plasma membranes, different methods were applied (immunocytochemistry, immunofluorescence, immunoblotting) using the monoclonal antibodies 265/F4 and C 219. These methods all revealed an increased expression of the glycoprotein Mr 170 kd in the multidrug-resistant cell lines. To determine whether multidrug DNA sequences were expressed in the resistant cell lines, slot blots and Northern blots with RNA of sensitive and resistant cells were performed using the clones pDR 7.8 and pcDR 1.5. Elevated RNA levels were detected in all resistant cell lines.