Obesity is associated with breast cancer aggressiveness and drug resistance. Although the underlying mechanisms are unknown, recent studies indicated that exosomes have a principal contributory role in obesity-associated metabolic complications. Hence, we investigated whether obesity can mediate breast cancer progression and resistance to tamoxifen by plasma-derived-exosomes from obese women or not. Plasma exosomes isolated from five normal-weight (N-Exo) and five obese women (O-Exo) were characterized for size, zeta potential, and CD63 expression. After the treatment of MCF-7 cells with N-Exo and O-Exo, cell proliferation, migration, invasion as well as levels of MMP-9 and MMP-2 were evaluated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing, transwell, and zymography methods, respectively. For evaluating resistance to tamoxifen, the cell viability, apoptosis, and the p53 protein were evaluated using the MTT assay, flow cytometry, and western blot methods, respectively. Cell proliferation, migration, and invasion were significantly increased in the cells treated with O-Exo than untreated cells (p = .001, p = .018, p = .034, respectively). Levels of MMP-2 and MMP-9 were remarkably increased in the cells treated with O-Exo in comparison with ones treated with N-Exo (p = .040, p = .043, respectively). As for resistance to tamoxifen, O-Exo had significantly the greater anti-apoptotic effects in comparison with the N-Exo group (p = .013). Besides, p53 levels were significantly decreased in the cells treated with O-Exo than ones treated with N-Exo (p = .045). The cell viability was significantly more in cells treated with O-Exo in comparison with the cells only treated with tamoxifen (p = .040). Our findings demonstrated that circulating exosomes derived from obese women could lead to tumorigenesis and tamoxifen resistance in breast cancer cells. However, more studies are needed to establish this notion.

中文翻译：

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肥胖女性血浆循环外泌体对MCF-7细胞肿瘤发生和他莫昔芬耐药性的影响

肥胖与乳腺癌侵袭性和耐药性有关。尽管潜在机制尚不清楚，但最近的研究表明外泌体在肥胖相关的代谢并发症中起主要作用。因此，我们研究了肥胖是否可以通过来自肥胖女性的血浆衍生外泌体介导乳腺癌进展和对他莫昔芬的抵抗。从五名正常体重 (N-Exo) 和五名肥胖女性 (O-Exo) 中分离的血浆外泌体具有大小、zeta 电位和 CD63 表达的特征。用 N-Exo 和 O-Exo 处理 MCF-7 细胞后，通过 3-(4,5-Dimethylthiazol-2- yl)-2,5-二苯基溴化四唑 (MTT) 测定、伤口愈合、transwell 和酶谱法，分别。为了评估对他莫昔芬的抗性，分别使用 MTT 测定、流式细胞术和蛋白质印迹方法评估细胞活力、细胞凋亡和 p53 蛋白。与未处理的细胞相比，用 O-Exo 处理的细胞的细胞增殖、迁移和侵袭显着增加（分别为 p = .001、p = .018、p = .034）。与用 N-Exo 处理的细胞相比，用 O-Exo 处理的细胞中 MMP-2 和 MMP-9 的水平显着增加（分别为 p = .040，p = .043）。至于对他莫昔芬的抗性，与 N-Exo 组相比，O-Exo 具有显着更大的抗凋亡作用 (p = .013)。此外，与用 N-Exo 处理的细胞相比，用 O-Exo 处理的细胞中 p53 水平显着降低（p = .045）。与仅用他莫昔芬处理的细胞相比，用 O-Exo 处理的细胞的细胞活力明显更高（p = .040）。我们的研究结果表明，来自肥胖女性的循环外泌体可能导致乳腺癌细胞的肿瘤发生和他莫昔芬耐药。然而，需要更多的研究来建立这个概念。