加用依他尼酸增强来那度胺和沙利度胺的体内疗效。

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

机构信息

Center for Integrated Oncoogy (CIO), Department of Internal Medicine III, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.

出版信息

In Vivo. 2011 May-Jun;25(3):325-33.

PMID:21576405

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.

摘要

背景

最近证实依他尼酸（EA）可抑制骨髓瘤中的 Wnt/β 连环蛋白信号通路。

材料和方法

本研究在小鼠骨髓瘤模型中体外和体内研究了 EA 的抗肿瘤作用。

结果

EA 在不同的人源和鼠源骨髓瘤和淋巴瘤细胞系以及人原代细胞中表现出明显的促凋亡活性。此外，当 EA 添加到淋巴瘤细胞中时，β-连环蛋白表达下调。在体内，与未治疗的小鼠相比，用 EA 治疗的小鼠的肿瘤生长和总生存期明显降低。有趣的是，体外实验中，与单独应用相比，来那度胺联合 EA 具有显著的相加作用。