Increased in vivo efficacy of lenalidomide and thalidomide by addition of ethacrynic acid

Abstract

Background: It was recently confirmed that ethacrynic acid (EA) inhibits Wnt/beta catenin signalling in myeloma.

Materials and methods: This study investigated the antitumor effect of EA in vitro and in vivo in a murine myeloma model.

Results: EA demonstrated major apoptotic activity in different human and murine myeloma and lymphoma cell lines, as well as in human primary cells. In addition β-catenin expression was down-regulated when EA was added to lymphoma cells. In vivo, tumor growth, as well as overall survival, was significantly reduced in mice treated with EA as compared to untreated mice. Interestingly, in vitro, a significant additive effect was seen with the combination of lenalidomide plus EA as compared to single applications.

Conclusion: These results reveal a significant selective induction of apoptosis by EA and suggest a significant in vivo effect against myeloma.