Multidrug resistant variants of two human osteosarcoma cell lines (U-2 OS and Saos-2) were selected by continuous exposure to doxorubicin. The in vitro and in vivo growth characteristics of these sublines as well as the expression of osteoblastic markers and of some surface antigens were analyzed. Resistant variants showed a higher doubling time and a lower cloning efficiency, and a lower metastatic ability after i.v. injection than corresponding parental cell lines. All the sublines showed overexpression of p-glycoprotein (referred to as pl70). The level of expression of this protein in the different cell lines was directly related to the degree of resistance as shown by the in vitro sensitivity to doxorubicin and other multidrug-related drugs. In sublines showing the highest levels of resistance (over 300-fold), pl70 overexpression was associated with mdr 1 gene amplification. These are the first multidrug resistant human osteosarcoma cell lines ever reported. They may be used as a model for further investigations into the mechanisms of drug resistance in osteosarcoma and as a standard for the assessment of chemosensitivity in clinical samples.
|Number of pages||7|
|Publication status||Published - 1993|
- Multidrug resistance
ASJC Scopus subject areas
- Cancer Research