Breast cancer is the most commonly diagnosed cancer among women, and its metastasis to distant organs accounts for the majority of death. Eriocalyxin B (Eri B), an ent-kaurane diterpenoid isolating from Isodon eriocalyx var. laxiflora, has previously been reported to have anti-tumor and anti-angiogenic effects in breast cancer. Here, we investigated the effect of Eri B on cell migration and adhesion in triple negative breast cancer (TNBC) cells, as well as aldehyde dehydrogenases 1 family member A1 (ALDH1A1) expression, colony- and sphere-formation in cancer stem cell (CSC) enriched MDA-MB-231 cells. The in vivo anti-metastatic activities of Eri B were determined in 3 different breast tumor-bearing mouse models. Our results indicated that Eri B inhibited TNBC cell migration and adhesion to extracellular matrix proteins, and also reduced ALDH1A1 expression and colony formation in CSC-enriched MDA-MB-231 cells. The metastasis-related pathways, such as epidermal growth factor receptor/ mitogen-activated protein kinase kinases 1/2/ extracellular regulated protein kinase signaling altered by Eri B was firstly shown in MDA-MB-231 cells. The potent anti-metastatic efficacies of Eri B were demonstrated in breast xenograft-bearing mice and syngeneic breast tumor-bearing mice. Gut microbiome analysis results revealed the change in the diversity and composition of microbiome after Eri B treatment, and the potential pathways that are involved in the anti-cancer efficacy of Eri B. In conclusion, Eri B was shown to inhibit breast cancer metastasis in both in vitro and in vivo models. Our findings further support the development of Eri B as an anti­metastatic agent for breast cancer.

乳腺癌是女性中最常被诊断出的癌症，其向远处器官的转移占死亡的大部分。Eriocalyxin B (Eri B)，一种从Isodon eriocalyx var. 中分离出来的ent -kaurane 二萜类化合物。laxiflora以前曾被报道在乳腺癌中具有抗肿瘤和抗血管生成作用。在这里，我们研究了 Eri B 对三阴性乳腺癌 (TNBC) 细胞迁移和粘附的影响，以及醛脱氢酶 1 家族成员 A1 (ALDH1A1) 表达、癌症干细胞 (CSC) 中的集落和球体形成) 丰富的 MDA-MB-231 细胞。在体内在 3 种不同的荷瘤小鼠模型中测定了 Eri B 的抗转移活性。我们的结果表明，Eri B 抑制了 TNBC 细胞迁移和与细胞外基质蛋白的粘附，并且还减少了富含 CSC 的 MDA-MB-231 细胞中的 ALDH1A1 表达和集落形成。Eri B 改变的表皮生长因子受体/丝裂原活化蛋白激酶激酶 1/2/细胞外调节蛋白激酶信号转导等转移相关通路首次在 MDA-MB-231 细胞中显示。Eri B 的有效抗转移功效在携带异种移植物的乳房小鼠和携带同源乳腺肿瘤的小鼠中得到证实。肠道微生物组分析结果揭示了 Eri B 治疗后微生物组多样性和组成的变化，体外和体内模型。我们的研究结果进一步支持将 Eri B 开发为乳腺癌的抗转移剂。