DEVELOPMENT AND CHARACTERIZATION OF AN ADRIAMYCIN-RESISTANT SW480 HUMAN COLON ADENOCARCINOMA CELL-LINE

An adriamycin resistant Sw480 human colon adenocarcinoma cell line (Sw480 Adr) was developed. Characteristics of the Sw480 Adr cells were compared with that of the parent Sw480 (Sw480 WT) cell line. Sw480 Adr cells were cross-resistant to mitoxantrone but not to cisplatin. Glutathione S-transferase enzyme activity as well as glutathione S-transferase pi content were increased 1.5 fold in the resistant cells, whereas P-170 glycoprotein content was increased several hundredfold. Sw480 Adr cells could be partly resensitised towards adriamycin by prior incubation with verapamil (1.65-3.3 mug/ml) and completely resensitised by cyclosporin A (2.5-5.0 mug/ml). Incubation of Sw480 Adr cells with various concentrations of adriamycin (200-1600 nM) during one week, did not change the P-170 glycoprotein levels. In addition, Sw480 Adr cells cultured in adriamycin-free medium for ten weeks (and passaged each week), showed no significant change in P-170 glycoprotein content. These results indicate that the most important mechanism for adriamycin resistance in Sw480 Adr human colon adenocarcinoma cells is overexpression of the P-170 glycoprotein, an ATP-driven drug efflux pump located in the plasma membrane. This overexpression of the P-170 glycoprotein in Sw480 Adr cells does not seem to be reversible.