Brassinin,一种来源于十字花科蔬菜的植物抗毒素,据报道在多种癌症类型中表现出抗癌活性。然而,其对三阴性乳腺癌(TNBC)发展的影响及潜在机制至今尚未阐明.在这项研究中,我们在体外证明,与肿瘤微环境的其他细胞类型相比,油菜素优先降低内皮细胞(EC)的活力,包括TNBC细胞,周细胞,和成纤维细胞。此外,在非细胞毒性剂量的油菜素显著抑制增殖,迁移,管形成,和ECs的球状体发芽。它还在离体主动脉环测定和体内基质胶塞测定中有效抑制血管生成。每日腹腔注射油菜素显著减小肿瘤大小,微血管密度,以及TNBC背侧皮褶腔模型中肿瘤微血管的灌注。机制分析表明,油菜素选择性地刺激ECs中Tie2和成纤维细胞生长因子受体1的降解,导致AKT和细胞外信号调节激酶途径的下调。这些发现证明了油菜素的优先和有效的抗血管生成活性,这可能是其抗肿瘤作用的主要机制。因此,这种植物化学物质代表了未来TNBC抗血管生成治疗的有希望的候选者。
Brassinin, a phytoalexin derived from cruciferous vegetables, has been reported to exhibit anti-cancer activity in multiple cancer types. However, its effects on triple-negative breast cancer (TNBC) development and the underlying mechanisms have not been elucidated so far. In this study, we demonstrated in vitro that
brassinin preferentially reduces the viability of endothelial cells (ECs) when compared to other cell types of the tumor microenvironment, including TNBC cells, pericytes, and fibroblasts. Moreover,
brassinin at non-cytotoxic doses significantly suppressed the proliferation, migration, tube formation, and spheroid sprouting of ECs. It also efficiently inhibited angiogenesis in an ex-vivo aortic ring assay and an in-vivo Matrigel plug assay. Daily intraperitoneal injection of
brassinin significantly reduced tumor size, microvessel density, as well as the perfusion of tumor microvessels in a dorsal skinfold chamber model of TNBC. Mechanistic analyses showed that brassinin selectively stimulates the degradation of Tie2 and fibroblast growth factor receptor 1 in ECs, leading to the down-regulation of the AKT and extracellular signal-regulated kinase pathways. These findings demonstrate a preferential and potent anti-angiogenic activity of
brassinin, which may be the main mechanism of its anti-tumor action. Accordingly, this phytochemical represents a promising candidate for the future anti-angiogenic treatment of TNBC.