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Cellular resistance to mitomycin C is associated with overexpression of MDR-1 in a urothelial cancer cell line (MGH-U1)

Hayes, M.C., Birch, B.R., Cooper, A.J. and Primrose, J.N. (2001) Cellular resistance to mitomycin C is associated with overexpression of MDR-1 in a urothelial cancer cell line (MGH-U1) BJU International, 87, (3), pp. 245-250. (doi:10.1046/j.1464-410x.2001.02027.x).

Record type: Article


Objective: to compare multidrug resistance (MDR)-1 and MDR-3 gene expression in a new urothelial cancer cell line (MGHU-1, with resistance to mitomycin C) against controls and the established (epirubicin-resistant) MDR clone, and to correlate MDR with cytotoxicity data.
Materials and methods: resistance to mitomycin C was induced by the long-term exposure of wild-type MGHU-1 cells to increasing concentrations (20–400 nmol/L) of mitomycin C. The cytotoxicity of mitomycin C or epirubicin was then compared in MGHU-1, MGHU-MMC (mitomycin C-resistant) and MGHU-1R (established MDR) cells, using the tetrazolium biomass assay. The expression of MDR-1 and -3 was investigated by the reverse transcriptase-polymerase chain reaction, using cDNA-specific primers after titration, and compared with DNA and negative controls.
Results: MDR-1 and -3 were significantly and equally overexpressed in MGHU-1R, and associated with a dramatic increase in the 50% inhibitory drug concentration (P < 0.001) for mitomycin C and epirubicin against controls. In MGHU-MMC, the overexpression of MDR-1 was three times greater than that of MDR-3. The cytotoxicity profile for both agents was very similar to that of MGHU-1R. Trace amounts of MDR-1, but not MDR-3, were identified in the MGHU-1 wild-type.
Conclusions: Urothelial cancer cell resistance to mitomycin C is associated with cross-resistance to epirubicin and overexpression of MDR-1, suggesting that mitomycin C falls within the MDR category. Clinical application of this methodology may allow patients to be identified who are unlikely to benefit from intravesical chemotherapy.

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Published date: 2001


Local EPrints ID: 26379
ISSN: 1464-4096
PURE UUID: 119b9480-8536-44fa-9eb2-c062d6509946
ORCID for J.N. Primrose: ORCID iD

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Date deposited: 24 Apr 2006
Last modified: 11 Jul 2017 09:46

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Author: M.C. Hayes
Author: B.R. Birch
Author: A.J. Cooper
Author: J.N. Primrose ORCID iD

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