Cardioprotective effect of paeonol against epirubicin-induced heart injury via regulating miR-1 and PI3K/AKT pathway

被引:56
作者
Wu, Jing [1 ]
Sun, Chao [1 ]
Wang, Ruoyi [2 ]
Li, Juan [1 ]
Zhou, Meng [1 ]
Yan, Mi [1 ]
Xue, Xia [1 ]
Wang, Chuanxin [3 ]
机构
[1] Shandong Univ, Hosp 2, Dept Pharm, Jinan, Shandong, Peoples R China
[2] Shandong Univ, Hosp 2, Pediat Surg, Jinan, Shandong, Peoples R China
[3] Shandong Univ, Hosp 2, 247 Beiyuan Rd, Jinan 250033, Peoples R China
基金
中国国家自然科学基金;
关键词
Epirubicin; Paeonol; Cardiotoxicity; miR-1; PI3K/AKT; INDUCED CARDIOTOXICITY; MOLECULAR-MECHANISMS; BREAST-CANCER; AUTOPHAGY; DOXORUBICIN; CARDIOMYOPATHY; CARDIOMYOCYTES; APOPTOSIS;
D O I
10.1016/j.cbi.2018.02.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-kappa B pathways. In conclusion, paeonol effectively ameliorates myocardial injury by increasing miR-1 expression to suppress the PI3K/AKT/mTOR and NF-kappa B signalling pathways.
引用
收藏
页码:17 / 25
页数:9
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