多柔比星致心脏毒性的可能信号途径

Signal pathways in doxorubicin-induced cardiotoxicity

多柔比星(Dox)为临床常用的广谱、高效抗肿瘤药物,用于恶性淋巴瘤、实体瘤等多种癌症的治疗。然而,心脏毒性严重限制其临床应用。Dox诱发心脏毒性的作用机制十分复杂,其具体机制至今尚不清楚。Dox可明显上调心脏组织中ROS及TNF-α水平,引起心肌细胞内钙负载及线粒体细胞色素C释放,活化钙信号、p38MAPK、PI3K/Akt等多条信号途径。充分理解这些信号途径在Dox介导心脏毒性过程中的作用对于防治Dox心脏毒性具有重要的指导意义。本文就近年来Dox致心脏毒性的可能信号途径作简要综述。

Doxorubicin （Dox） is a broad spectrum and powerful anticancer drug while its use is severely restricted by its cardiotoxicity. Dox can upregulate the expression of reactive oxygen species （ROS） and TNF-α in vitro and in vivo, as well as elevate intracellular calcium level. Several signal pathways including ROS and calcium signaling, cytochrome C, p38 MAPK, PI3K/Akt are involved in the development of doxorubicin-induced cardiotoxicity, which may play a critical role though the precise biochemical mechanism still remains unclear. In this review, we will discuss the potential signal events in doxorubicin-induced cardiotoxicity. We hope it may be of great value in new drug discovery for preventing and curing doxorubicin-induced cardiotoxicity.