Glutathione-S-transferases and Chemotherapy Resistance of Hodgkin's Lymphoma Cell Lines

Abstract

Background: Glutathione-S-transferases (GSTs) are associated with multidrug resistance of tumor cells and are involved in drug detoxification and control of apoptosis. We analyzed the impact of GSTs on apoptosis of Hodgkin's lymphoma (HL) cells.

Materials and methods: Expression of GST isoforms in HL cell lines was assessed by analysis of DNA microarray data and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of the GST inhibitor ethacrynic acid (EA) on HL cell survival was analyzed in vitro.

Results: DNA microarray analysis and qRT-PCR analysis demonstrated higher expression of GST isoforms in chemoresistant HL cells. Therefore, GSTs may contribute to chemoresistance of HL cells. Incubation of GST-expressing chemoresistant L-1236 HL cells with EA significantly enhanced the activity of cisplatin against these cells.

Conclusion: Our data suggest that the combined treatment with chemotherapy and GST inhibitors such as EA might be an interesting option for patients with chemoresistant HL.

Keywords: Hodgkin's lymphoma; chemotherapy; ethacrynic acid; glutathione-S-transferases.