Characterization of chemoresistance mechanisms in a series of cisplatin-resistant transitional carcinoma cell lines

We explored the mechanisms of cisplatin resistance in a series of bladder t ransitional carcinoma cells that are either sensitive ol progressively resi stant to cisplatin. Resistant lines were raised by chronic exposure of the parental cells to progressively increased concentrations of cisplatin. The cisplatin IC50s of the sensitive and the three resistant cells were 4.3, 25 .0, 40.4, and 52.2 muM, respectively. The expressions of glutathione S-tran sferase pi (GST-pi) and multidrug resistance-associated protein (MRP) were enhanced in a dose-response manner as cells acquired progressive cisplatin resistance. Expression of mdr-1 transcript was detected in the three resist ant lines but not in the sensitive line. Glutathione contents were increase d in resistant cells, yet the the end of increase did not reach statistical significance (p = 0.061). In conclusion, transitional carcinoma cells may gain cisplatin resistance through multiple pathways including up-regulation of GST-pi, MRP and possibly mdr-1. Glutathione contents may play a less si gnificant role in cisplatin chemoresistance.