Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
The Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
Proteomics. 2023 Sep;23(18):e2200482. doi: 10.1002/pmic.202200482. Epub 2023 Jun 27.
Metastatic triple-negative breast cancer (TNBC) has a low 5-year survival rate of below 30% with systemic chemotherapy being the most widely used treatment. Bovine milk-derived extracellular vesicles (MEVs) have been previously demonstrated to have anti-cancer attributes. In this study, we isolated bovine MEVs from commercial milk and characterised them according to MISEV guidelines. Bovine MEVs sensitised TNBC cells to doxorubicin, resulting in reduced metabolic potential and cell-viability. Label-free quantitative proteomics of cells treated with MEVs and/or doxorubicin suggested that combinatorial treatment depleted various pro-tumorigenic interferon-inducible gene products and proteins with metabolic function, previously identified as therapeutic targets in TNBC. Combinatorial treatment also led to reduced abundance of various STAT proteins and their downstream oncogenic targets with roles in cell-cycle and apoptosis. Taken together, this study highlights the ability of bovine MEVs to sensitise TNBC cells to standard-of-care therapeutic drug doxorubicin, paving the way for novel treatment regimens.
转移性三阴性乳腺癌（TNBC）的 5 年生存率低于 30%，系统化疗是最广泛使用的治疗方法。牛乳来源的细胞外囊泡（MEVs）先前已被证明具有抗癌特性。在这项研究中，我们从商业牛奶中分离出牛 MEVs，并根据 MISEV 指南对其进行了表征。牛 MEVs 使 TNBC 细胞对多柔比星敏感，导致代谢潜力和细胞活力降低。用 MEVs 和/或多柔比星处理的细胞的无标记定量蛋白质组学表明，联合治疗耗尽了各种促肿瘤干扰素诱导基因产物和具有代谢功能的蛋白质，这些蛋白质先前被确定为 TNBC 的治疗靶点。联合治疗还导致各种 STAT 蛋白及其在细胞周期和凋亡中发挥作用的下游致癌靶蛋白的丰度降低。总之，这项研究强调了牛 MEVs 使 TNBC 细胞对标准治疗药物多柔比星敏感的能力，为新的治疗方案铺平了道路。
