The expression of mdr-1-related gp-170 and its correlation with anthracycline resistance in renal cell carcinoma cell lines and multidrug-resistant sublines.

Abstract

To clarify the role of the membranous glycoprotein gp-170 in renal cell carcinoma (RCC) cell lines and their multidrug resistant (MDR) sublines. and to correlate gp-170 with the natural and acquired drug resistance of these cell lines to anthracyclines. The expression of gp-170 in five cultured RCC cell lines and serial RCC8701 MDR sublines was analysed by immunofluorescent flow cytometry. The chemosensitivity of these tumour cells to the anthracycline anticancer drugs adriamycin and epirubicin was measured using the microplate tetrazolium (MTT) cytotoxicity assay, and the results correlated with gp-170 expression. All six natural RCC cell lines showed a variably increased expression of gp-170, with the A704 and Caki-1 cell lines the highest. In contrast, gp-170 expression increased and then was suppressed in acquired MDR sublines of RCC8701 cultured in increasing concentrations of adriamycin. The A704 and Caki-1 cells were much more resistant to adriamycin and epirubicin than the A498, ACHN and RCC8701 cell lines, in parallel with the expression of gp-170. The resistant cell line cultured long-term in 800 ng/mL adriamycin, RCC8701/ADR800, was 122 times more resistant to adriamycin and 238 times more resistant to epirubicin than the parent cell line: the pattern differed from that in native RCC cell lines and was unrelated to the expression of gp-170. Membranous gp-170 plays an important role in MDR of native RCC cell lines, while acquired MDR cells have different mechanisms of obtaining drug resistance in addition to gp-170. This phenomenon may be applicable to the clinical treatment of patients newly diagnosed with RCC or those with disease refractory to chemotherapy.