DDX3X alleviates doxorubicin-induced cardiotoxicity by regulating Wnt/β-catenin signaling pathway in an in vitro model.
DDX3X alleviates doxorubicin-induced cardiotoxicity by regulating Wnt/β-catenin signaling pathway in an in vitro model.
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DDX3X 在体外模型中通过调节 Wnt/β-catenin 信号通路减轻阿霉素诱导的心脏毒性
DOI：
10.1002/jbt.23077
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发表时间：
2022-08
影响因子：
3.6
通讯作者：
Hao, Enkui
中科院分区：
文献类型：
--
作者：
Feng, Dandan;Li, Jiang;Guo, Liang;Liu, Jing;Wang, Shaochen;Ma, Xiuyuan;Song, Yunxuan;Liu, Ju;Hao, Enkui
多柔比星（Dox）的心脏毒性引起的危及生命的不良反应限制了其临床应用。DDX 3X已被证明参与多种生理过程，并作为Wnt/β-catenin信号传导的调节剂。然而，DDX 3X在Dox诱导的心脏毒性（DIC）中的作用仍不清楚。在这项研究中，我们发现DDX 3X表达在用Dox处理的H9 c2心肌细胞中显著降低。敲除Ddx 3x和RK-33（DDX 3X ATP酶活性抑制剂）预处理加重了Dox处理诱导的心肌细胞凋亡和线粒体功能障碍。相反，Ddx 3x过表达改善DIC反应。此外，在用Dox处理的心肌细胞中Wnt/β-catenin信号传导被抑制，但这种抑制被Ddx 3x过表达逆转。总之，这项研究表明，DDX 3X通过激活Wnt/β-catenin信号传导在DIC中发挥保护作用。
The life‐threatening adverse effects of doxorubicin (Dox) caused by its cardiotoxic properties limit its clinical application. DDX3X has been shown to participate in a variety of physiological processes, and it acts as a regulator of Wnt/β‐catenin signaling. However, the role of DDX3X in Dox‐induced cardiotoxicity (DIC) remains unclear. In this study, we found that DDX3X expression was significantly decreased in H9c2 cardiomyocytes treated with Dox. Ddx3x knockdown and RK‐33 (DDX3X ATPase activity inhibitor) pretreatment exacerbated cardiomyocyte apoptosis and mitochondrial dysfunction induced by Dox treatment. In contrast, Ddx3x overexpression ameliorated the DIC response. Moreover, Wnt/β‐catenin signaling in cardiomyocytes treated with Dox was suppressed, but this suppression was reversed by Ddx3x overexpression. Overall, this study demonstrated that DDX3X plays a protective role in DIC by activating Wnt/β‐catenin signaling.
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