Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Gerontology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
IUBMB Life. 2019 Oct;71(10):1465-1474. doi: 10.1002/iub.2058. Epub 2019 May 3.
Indirubin is widely used as the active component of "Dangui Luhui Wan" in ancient China. However, its effects against the osteosarcoma (OS), the most common primary malignancy, are still unknown. In our present study, we investigated the effects of the Indirubin-3'-monoxime (I3M), a derivative of indirubin with better water solubility, against the OS cells. We found I3M inhibited OS cell proliferation in a dose-dependent manner. Flow cytometry assays showed that I3M could not only induce OS cell apoptosis in a time- and dose-dependent manner but also regulate the cell cycle distribution. Additionally, we demonstrated that several Bcl-2 family members, cyclin-dependent kinases (CDKs) and cyclins contributed to this process. Furthermore, out data verified that I3M suppressed OS cell migration and invasion by decreasing MMP-2 and MMP-9 levels. Moreover, survivin and focal adhesion kinase (FAK) might play important roles in the anti-OS effects of I3M. The administration of I3M also inhibited the OS cell growth in mice. Taken together, our results indicated the inhibitory effects of I3M against human OS and thus might be an efficient candidate for OS chemotherapy.
靛玉红在古方“当归六黄丸”中被广泛用作有效成分。然而，其对骨肉瘤（OS）这种最常见的原发性恶性肿瘤的作用仍不清楚。在我们目前的研究中，我们研究了靛玉红-3'-单肟（I3M）对 OS 细胞的作用。I3M 是靛玉红的一种水溶性更好的衍生物，我们发现 I3M 能够以剂量依赖的方式抑制 OS 细胞的增殖。流式细胞术检测结果表明，I3M 不仅能够以时间和剂量依赖的方式诱导 OS 细胞凋亡，还能够调节细胞周期分布。此外，我们证明了几个 Bcl-2 家族成员、细胞周期蛋白依赖性激酶（CDKs）和细胞周期蛋白参与了这一过程。此外，我们的数据证实 I3M 通过降低 MMP-2 和 MMP-9 水平抑制 OS 细胞迁移和侵袭。此外，生存素和黏着斑激酶（FAK）可能在 I3M 的抗 OS 作用中发挥重要作用。I3M 的给药也抑制了小鼠中 OS 细胞的生长。综上所述，我们的研究结果表明 I3M 对人骨肉瘤具有抑制作用，因此可能是骨肉瘤化疗的有效候选药物。
