多柔比星对成纤维细胞自噬的影响

Anna Shuey, Conner Patricelli, Julia T Oxford, Xinzhu Pu
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引用次数: 0

摘要

研究目的多柔比星(DOX)是一种高效的化疗药物,用于治疗许多成人和儿童癌症,如实体瘤、白血病、淋巴瘤和乳腺癌。尽管心脏毒性是 DOX 最突出的副作用,但它也会对心脏、肝脏、大脑或肾脏等多个器官造成伤害。在这项研究中,我们研究了 DOX 对两种不同小鼠成纤维细胞自噬活性的潜在影响:方法:用 DOX 处理小鼠胚胎成纤维细胞(NIH3T3)和小鼠原代心脏成纤维细胞(CFs),以评估两种常用自噬蛋白标记物 LC3II 和 p62 的表达变化。我们还研究了 DOX 对编码自噬分子机制和调控因子的关键基因表达的影响,这些基因是对细胞外和细胞内信号的反应:结果:我们观察到,DOX 处理 NIH3T3 细胞后,LC3II 水平升高,p62 水平降低。然而,在原代心脏成纤维细胞中没有观察到类似的效应。此外,在 NIH3T3 细胞中,DOX 处理诱导了大量参与自噬的基因上调,但在原代心脏成纤维细胞中却没有:综上所述,这些结果表明,DOX能以细胞特异性的方式上调成纤维细胞的自噬。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of doxorubicin on autophagy in fibroblasts.

Objectives: Doxorubicin (DOX) is a highly effective chemotherapeutic used to treat many adult and pediatric cancers, such as solid tumors, leukemia, lymphomas and breast cancer. It can also cause injuries to multiple organs, including the heart, liver, and brain or kidney, although cardiotoxicity is the most prominent side effect of DOX. In this study, we examined the potential effects of DOX on autophagy activity in two different mouse fibroblasts.Methods: Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX to assess changes in the expression of two commonly used autophagy protein markers, LC3II and p62. We also examined the effects of DOX the on expression of key genes that encode components of the molecular machinery and regulators modulating autophagy in response to both extracellular and intracellular signals.Results: We observed that LC3II levels increased and p62 levels decreased following the DOX treatment in NIH3T3 cells. However, similar effects were not observed in primary cardiac fibroblasts. In addition, DOX treatment induced the upregulation of a significant number of genes involved in autophagy in NIH3T3 cells, but not in primary cardiac fibroblasts.Conclusions: Taken together, these results indicate that DOX upregulates autophagy in fibroblasts in a cell-specific manner.

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