Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer.
Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer.
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维生素D对阿霉素诱导的三重阴性乳腺癌中心脏毒性的细胞保护作用。
DOI：
10.3390/ijms22147439
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发表时间：
2021-07-12
影响因子：
5.6
通讯作者：
Gassman NR
中科院分区：
文献类型：
--
作者：
Lee KJ;Wright G;Bryant H;Wiggins LA;Dal Zotto VL;Schuler M;Malozzi C;Cohen MV;Gassman NR
背景资料：多柔比星（Dox）是三阴性乳腺癌（TNBC）的一线治疗药物，但其使用可能受到活性氧产生介导的心脏毒性的限制。我们评估了维生素D是否可以预防小鼠TNBC模型中Dox诱导的心脏毒性。研究方法：雌性Balb/c小鼠接受含维生素D3的啮齿动物饲料（1500 IU/kg;溶媒）或补充额外维生素D3的饲料（总计11，500 IU/kg）。给小鼠接种TNBC肿瘤并用腹膜内Dox（6或10 mg/kg）处理。经胸超声心动图评价心功能。采用免疫组织化学和免疫印迹法评价心脏组织中4-羟基壬烯醛、NAD（P）H醌氧化还原酶（NQO 1）、C-MYC和动力蛋白相关蛋白1（DRP 1）磷酸化水平。结果如下：在第15至18天，平均射血分数、每搏输出量和缩短分数在用维生素D + Dox（10 mg/kg）处理的小鼠与载体处理的小鼠之间相似，但在用维生素D + Dox（10 mg/kg）处理的小鼠中显著大于用Dox（10 mg/kg）处理的小鼠。Dox（10 mg/kg）增加了4-羟基壬烯醛、NQO 1、C-MYC和DRP 1在丝氨酸616处磷酸化的心脏组织水平，但维生素D + Dox（10 mg/kg）未观察到这些增加。用Dox（10 mg/kg）和维生素D + Dox（10 mg/kg）观察到肿瘤体积减小。结论：维生素D补充通过减少活性氧和线粒体损伤降低了Dox诱导的心脏毒性，并且没有降低Dox对TNBC的抗癌功效。
Background: Doxorubicin (Dox) is a first-line treatment for triple negative breast cancer (TNBC), but its use may be limited by its cardiotoxicity mediated by the production of reactive oxygen species. We evaluated whether vitamin D may prevent Dox-induced cardiotoxicity in a mouse TNBC model. Methods: Female Balb/c mice received rodent chow with vitamin D3 (1500 IU/kg; vehicle) or chow supplemented with additional vitamin D3 (total, 11,500 IU/kg). the mice were inoculated with TNBC tumors and treated with intraperitoneal Dox (6 or 10 mg/kg). Cardiac function was evaluated with transthoracic echocardiography. The cardiac tissue was evaluated with immunohistochemistry and immunoblot for levels of 4-hydroxynonenal, NAD(P)H quinone oxidoreductase (NQO1), C-MYC, and dynamin-related protein 1 (DRP1) phosphorylation. Results: At 15 to 18 days, the mean ejection fraction, stroke volume, and fractional shortening were similar between the mice treated with vitamin D + Dox (10 mg/kg) vs. vehicle but significantly greater in mice treated with vitamin D + Dox (10 mg/kg) vs. Dox (10 mg/kg). Dox (10 mg/kg) increased the cardiac tissue levels of 4-hydroxynonenal, NQO1, C-MYC, and DRP1 phosphorylation at serine 616, but these increases were not observed with vitamin D + Dox (10 mg/kg). A decreased tumor volume was observed with Dox (10 mg/kg) and vitamin D + Dox (10 mg/kg). Conclusions: Vitamin D supplementation decreased Dox-induced cardiotoxicity by decreasing the reactive oxygen species and mitochondrial damage, and did not decrease the anticancer efficacy of Dox against TNBC.
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影响因子：
5.3
作者：
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影响因子：
3.2
作者：
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DOI：
10.1152/ajpheart.00528.2017
发表时间：
2018-02-01
影响因子：
4.8
作者：
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影响因子：
4.8
作者：
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