ESTABLISHMENT AND CHARACTERIZATION OF MULTIDRUG-RESISTANT HUMAN OSTEOSARCOMA CELL-LINES

Multidrug resistant variants of two human osteosarcoma cell lines (U-2 OS and Saos-2) were selected by continuous exposure to doxorubicin. T he in vitro and in vivo growth characteristics of these sublines as we ll as the expression of osteoblastic markers and of some surface antig ens were analyzed. Resistant variants showed a higher doubling time an d a lower cloning efficiency, and a lower metastatic ability after i.v . injection than corresponding parental cell lines. All the sublines s howed overexpression of p-glycoprotein (referred to as p170). The leve l of expression of this protein in the different cell lines was direct ly related to the degree of resistance as shown by the in vitro sensit ivity to doxorubicin and other multidrug-related drugs. In sublines sh owing the highest levels of resistance (over 300-fold), p170 overexpre ssion was associated with mdr 1 gene amplification. These are the firs t multidrug resistant human osteosarcoma cell lines ever reported. The y may be used as a model for further investigations into the mechanism s of drug resistance in osteosarcoma and as a standard for the assessm ent of chemosensitivity in clinical samples.