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Updated: May 28, 2026

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确定多克索鲁比和卡菲尔佐米布诱导心脏毒性的常见途径:转录组和表观遗传分析

Conagh Kelly^1,2,3, Dylan J Kiltschewskij^1,4, Angeline J W Leong^2,3,5

¹School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2305, Australia.

Scientific reports

|February 5, 2025

概括

与癌症治疗相关的心血管毒性是一个主要问题. 这项研究揭示了多克索鲁比和卡菲尔佐米布之间的共享心脏毒性机制,确定了癌症患者心脏功能障碍的潜在治疗标.

科学领域:

心血管研究的心血管研究.
在瘤学瘤学.
分子生物学分子生物学

背景情况:

与癌症治疗相关的心血管毒性 (CTR-CVT) 是癌症幸存者患病和死亡的重要原因.
不同类化学疗法的心脏毒性背后的机制在很大程度上是未知的.
已知 doxorubicin 和 carfilzomib 诱导心力衰竭,需要对它们的共同和独特心脏毒性途径进行调查.

研究的目的:

调查多克索鲁比和卡菲尔佐米布诱导的心脏功能障碍的共同和差异性机制.
为了确定新的治疗策略的潜在重叠心脏毒性途径.
探索暴露于这些化疗剂的心肌细胞中的分子变化.

主要方法:

主要的人类心肌细胞样细胞 (HCM-ls) 暴露于多克索鲁比或卡菲尔佐米布.
评估了细胞活力和损伤.
使用MethylationEPIC数组分析了DNA甲基化模式.
基因表达特征通过RNA测序 (RNA-seq) 来确定.

主要成果:

多克索鲁比和卡菲尔佐米布都显著降低了HCM细胞活力,并导致细胞损伤.
观察到明显和常见的DNA甲基化变化,差异甲基化位置 (DMPs) 大约有12.9%的重叠.
RNA-seq确定了5643个常见失调的差异表达基因 (DEGs),PI3K-Akt信号通路被显著丰富.

结论:

doxorubicin 和 carfilzomib 在分子水平上具有共同的心脏毒性机制.
PI3K-Akt信号通路是关键的通用通路,涉及这些药物的心脏毒性.
识别这些共享途径为不同类型的抗癌药物减轻心血管毒性提供了潜在的治疗点.

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