The development of drug resistance during cancer chemotherapy is one of the principal causes of the failure of this treatment modality. We previously demonstrated that selenite can prevent the development of melphalan resistance in human ovarian tumor cells in vitro. In order to examine whether selenite can also have a preventive effect in vivo, we designed a system in which drug resistance can be induced in human ovarian tumors growing as xenografts in immunodeficient mice. The tumor-bearing animals were treated with melphalan, after which the tumors were removed and the cells were tested for sensitivity to melphalan in vitro. In this system a single treatment of the animals with melphalan was sufficient to induce the development of drug resistance. We tested the ability of selenite to prevent the development of resistance by administering it to the animals during the period of the melphalan treatment. We found that selenite in drinking water or administered subcutaneously had little or no effect on the development of resistance. However, when administered intraperitoneally, selenite completely prevented the development of drug resistance at doses as low as 0.75 mg Se/kg. These results suggest that selenium may be clinically useful in the prevention of drug resistance when administered along with a primary chemotherapeutic agent.
|Original language||English (US)|
|State||Published - Mar 20 1998|
All Science Journal Classification (ASJC) codes
- Molecular Biology