Ophiopogonin D, a steroidal glycoside extracted from the Traditional Chinese Medicine Ophiopogon japonicus, shows anti-tumor property in several lines of cancers; however, its effect on triple-negative breast cancer (TNBC) has not been investigated. In this study, the anti-metastatic effect of Ophiopogonin D in TNBC cells as well as the underlying mechanism in such process was explored. Ophiopogonin D dose-dependently decreased cell proliferation of MDA-MB-231 cells. Meanwhile, Ophiopogonin D significantly inhibited TGF-β1-induced metastatic behavior of MDA-MB-231 cells, including EMT, anoikis resistance as well as migration and invasion, via suppressing MMP-9 activity. Mechanically, Ophiopogonin D achieved its effect through efficiently abolishing ITGB1 expression, thus reducing the phosphorylation of FAK, Src and AKT, as well as upregulating nuclear β-catenin. ITGB1 overexpression partly recovered Ophiopogonin D's inhibitory effect on metastatic behavior via activating MMP-9. These results demonstrated that Ophiopogonin D could suppress TGF-β1-mediated metastatic behavior of MDA-MB-231 cells by regulating ITGB1/FAK/Src/AKT/β-catenin/MMP-9 signaling axis, which might provide new insight for the control of TNBC metastasis.

麦冬素 D 是一种从中药麦冬中提取的甾体糖苷，在多种癌症中显示出抗肿瘤特性；然而，尚未研究其对三阴性乳腺癌 (TNBC) 的影响。本研究探讨了麦冬素 D 在 TNBC 细胞中的抗转移作用以及该过程的潜在机制。麦冬素 D 剂量依赖性地降低 MDA-MB-231 细胞的细胞增殖。同时，麦冬素 D 显着抑制 TGF-β1 诱导的 MDA-MB-231 细胞转移行为，包括 EMT、失巢凋亡抵抗以及迁移和侵袭，通过抑制 MMP-9 活性。从机制上讲，麦冬素 D 通过有效消除 ITGB1 表达，从而降低 FAK、Src 和 AKT 的磷酸化，以及上调核 β-连环蛋白来实现其作用。ITGB1 过表达部分恢复了麦冬素 D通过激活 MMP-9对转移行为的抑制作用。这些结果表明麦冬素 D 可以通过调节 ITGB1/FAK/Src/AKT/β-catenin/MMP-9 信号轴来抑制 TGF-β1 介导的 MDA-MB-231 细胞的转移行为，这可能为控制提供新的见解TNBC 转移。