Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-03-02 , DOI: 10.1016/j.cbi.2018.02.035 Jing Wu , Chao Sun , Ruoyi Wang , Juan Li , Meng Zhou , Mi Yan , Xia Xue , Chuanxin Wang
Cardiotoxicity is a dose-dependent side effect of epirubicin that restricts its clinical utility in cancer chemotherapy. Paeonol is an active constituent with various biological activities, including the protection of antineoplastic-induced toxicities. In the present study, we investigated the protective effect of paeonol on epirubicin-induced cardiotoxicity and explored the underlying mechanism. A series of methods were used including a MTT assay, flow cytometry, echocardiography, TUNEL staining, a dual-luciferase reporter assay, immunofluorescence, RT-PCR and Western blotting. The results indicate that paeonol improves cardiac dysfunction, relieves histopathological changes, alleviates inflammation, reduces myocardial apoptosis and increases autophagy. Further studies suggest that paeonol upregulates the decreased expression of miR-1 caused by epirubicin and thus inhibits the activation of PI3K/AKT/mTOR and NF-κB pathways. In conclusion, paeonol effectively ameliorates myocardial injury by increasing miR-1 expression to suppress the PI3K/AKT/mTOR and NF-kB signalling pathways.
中文翻译:
丹皮酚通过调节miR-1和PI3K / AKT途径对表柔比星诱导的心脏损伤的心脏保护作用
心脏毒性是表柔比星的剂量依赖性副作用,它限制了其在癌症化学疗法中的临床应用。丹皮酚是具有多种生物学活性的活性成分,包括对抗肿瘤药诱导的毒性的保护。在本研究中,我们调查了丹皮酚对表柔比星诱导的心脏毒性的保护作用,并探讨了其潜在机制。使用了一系列方法,包括MTT分析,流式细胞仪,超声心动图,TUNEL染色,双荧光素酶报告基因分析,免疫荧光,RT-PCR和Western印迹。结果表明丹皮酚可改善心脏功能障碍,缓解组织病理学变化,减轻炎症,减少心肌细胞凋亡并增加自噬。进一步的研究表明,丹皮酚上调由表柔比星引起的miR-1表达降低,从而抑制PI3K / AKT / mTOR和NF-κB途径的激活。总之,丹皮酚可通过增加miR-1表达来抑制PI3K / AKT / mTOR和NF-kB信号通路,从而有效减轻心肌损伤。