DIFFERENTIAL MECHANISMS OF MULTIDRUG-RESISTANCE ARE EXPRESSED DURING STEPWISE SELECTION OF KB-3-1 CELLS WITH ADRIAMYCIN

A major limitation of cancer chemotherapy is development of resistance . In this study, we analyzed KB-3-1 cells and adriamycin-selected mult idrug resistant sublines KB-A1 and KB-A10 cells for mechanisms of resi stance. KB-A10 cells are 10-fold more resistant than KB-A1 cells but h ave lower P-glycoprotein. Of the known mechanisms of multidrug resista nce, topoisomerase II and lung-resistance-related protein were altered between the resistant cell lines. Glutathione-S-transferase activity and multidrug-resistance-related protein levels were higher in the res istant cell lines compared to the sensitive cells but were similar in KB-A1 and KB-A10 cells. Results indicate differential regulation of me chanisms of resistance with stepwise selection.