Selenite prevents the development of drug resistance in tumor cells in vitro

The development of drug resistance is the primary reason for the failure of chemotherapy as a treatment for human cancer. We have been investigating the potential applications of selenium compounds in the solution of this problem. In order to examine whether selenite can interfere with the development of drug resistance, we have designed a model system in which exposure of drug-sensitive A2780 human ovarian tumor cells to low concentrations of melphalan for 7 days results in a population of drug-resistant cells. These cells have higher levels of glutathione-S-transferase (GST) activity than the drug-sensitive parent cells; exposure of the cells to ethacrynic arid decreased their level of GST activity and also eliminated their resistance to melphalan. The inclusion of selenite during the melphalan exposure (at concentrations as low as 200 nM) effectively prevented the development of drug resistance, probably by preventing the melphalan-induced increase in GST activity. These results provide the first indication that selenite may be a useful agent for preventing the development of drug resistance during cancer chemotherapy.