乳腺癌（BRCA）是女性中最常见的癌症。阿霉素（ADR），也称为阿霉素（Dox），是BRCA患者常用的化疗药物，然而，肿瘤细胞对Dox产生耐药性的易感性严重限制了其临床应用。乳腺癌患者的一种新的有希望的治疗靶点是外泌体。本研究的目的是研究外泌体在调节 BRCA 耐药性中的作用。在这项研究中，通过差速离心从两种类型的细胞中提取外泌体。通过激光共聚焦显微镜、MTT 测定和 qRT-PCR 评估外泌体对耐药性的影响。使用 Lipofectamine 2000 将 miRNA 转染到细胞中，然后评估下游基因和耐药性变化。本研究有效地提取了 MCF-7 细胞 (MCF-7/exo) 和 MCF-7/ADR 细胞 (ADR/exo) 的外泌体。 ADR/exo 能够内吞 MCF-7 细胞，并使它们对 Dox 具有更强的抵抗力。此外，我们观察到与 MCF-7 和 MCF-7/exo 相比，MCF-7/ADR 和 ADR/exo 中 miR-34a-5p 表达存在显着差异。 miR-34a-5p靶基因中，NOTCH1表现出明显的负相关变化。此外，当 MCF-7/ADR 细胞中 miR-34a-5p 表达升高时，ADR/exo 中 miR-34a-5p 的表达也与 NOTCH1 一起增强，这意味着外泌体可能携带 miRNA 进出细胞，并且履行他们的职能。总之，外泌体可以通过调节 miR-34a-5p/NOTCH1 影响乳腺癌细胞的 Dox 耐药性。这些发现为研究乳腺癌肿瘤耐药原因和增强化疗疗效提供了新的见解。版权所有 © 2024。由 Elsevier Ltd 出版。

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.Copyright © 2024. Published by Elsevier Ltd.