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Updated: Jul 27, 2026

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver
Published on: July 31, 2016
Prevention of the development of melphalan resistance in vitro by selenite
P B Caffrey1, M Zhu, G D Frenkel
1Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Abstract:
Exposure of A2780 human ovarian tumor cells to a low concentration of melphalan in vitro for 7 d results in the development of melphalan resistance, which is dependent on elevated cellular levels of glutathione and glutathione S-transferase. The inclusion of selenite (at concentrations as low as 0.2 microM) during the exposure to melphalan completely prevented the development of resistance. Selenite did not prevent the melphalan-induced increase in glutathione, but it did prevent the increase in the activity of glutathione S-transferase. It also prevented the increase in the expression of the glutathione S-transferase gene, suggesting that this may be the mechanism by which it prevents the development of melphalan resistance. The results of this in vitro study suggest that selenite may prove to be useful in preventing the development of drug resistance in vivo.
Insights
Selenite supplementation prevented melphalan resistance in ovarian cancer cells by inhibiting glutathione S-transferase (GST) gene expression and activity. This suggests selenite could be a valuable tool in overcoming drug resistance in cancer therapy.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Melphalan resistance is a significant challenge in ovarian cancer treatment.
- Elevated glutathione (GSH) and glutathione S-transferase (GST) are key mechanisms of melphalan resistance.
- Novel strategies are needed to overcome drug resistance in cancer therapy.
Purpose of the Study:
- To investigate the effect of selenite on the development of melphalan resistance in A2780 human ovarian tumor cells.
- To elucidate the molecular mechanisms underlying selenite's potential to prevent drug resistance.
Main Methods:
- A2780 cells were exposed to melphalan in vitro for 7 days, with and without selenite.
- Cellular glutathione levels and GST activity were measured.
- GST gene expression was analyzed.
Main Results:
- Selenite (≥0.2 microM) completely prevented melphalan-induced resistance.
- Selenite did not affect melphalan-induced increases in glutathione levels.
- Selenite inhibited the increase in GST activity and prevented the upregulation of GST gene expression.
Conclusions:
- Selenite effectively prevents the development of melphalan resistance in ovarian cancer cells in vitro.
- The mechanism involves the inhibition of GST activity and gene expression, not glutathione levels.
- Selenite shows promise as a therapeutic agent to overcome drug resistance in vivo.
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