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

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