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

Objectives 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. Materials and methods 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. Results 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. Conclusion 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.

TPX2 in human clear cell renal carcinoma: Expression, function and prognostic significance

“…The most prevalent RCC subtype is clear cell, accounting for 85% of all RCC cases (3). Generally, RCC is resistant to conventional radiotherapy and chemotherapy (4,5). Prognosis for patients with metastatic RCC is poor, with a median survival time of 8 months and a 5-year survival rate of 10% (6).…”

Forkhead box J1 expression is upregulated and correlated with prognosis in patients with clear cell renal cell carcinoma

“…RCC is regarded as a localized disease in the early stages, however, 30% of patients with RCC that present with localized disease at the time of diagnosis develop metastatic disease within three years (2). Furthermore, the prognosis for metastatic RCC is poor (3) as RCC is resistant to traditional chemotherapy (4,5) and alternative therapeutic strategies for advanced RCC are limited. At present, novel strategies for the treatment of advanced RCC include molecular targeted therapy (6), monoclonal antibodies (7), immunotherapy (8) and the suppression of signaling pathways (9).…”

Enhanced antitumor activity of combinations of free and HPMA copolymer-bound drugs

“…This is due to gp-170, a membranous glycoprotein encoded by the MDR1 gene (Vugrin, 1987). The A498 cell line is a primary renal carcinoma cell line that expresses a moderate level of gp-170 (Yu et al, 1998). Moreover, A498 cell has been reported to express a functional wild-type p53.…”

“…These mechanisms lead to DNA strand breaks, DNA damage, and damage to cellular membranes, resulting in G 1 and G 2 cell cycle arrest and cell death (Fornari et al, 1994;Blagosklonny, 2002;Larsen et al, 2003). In vitro studies of DOX cytotoxicity toward renal carcinoma cell lines have shown that they are sensitive to DOX, especially the A498 cell line (Mertins et al, 2001;Yu et al, 1998). However, the usefulness of DOX is limited by side effects, particularly cumulative dose-dependent cardiotoxicity (Shan et al, 1996).…”