Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Anticancer Drugs. 2012 Feb;23(2):212-9. doi: 10.1097/CAD.0b013e32834e5592.
Tanshinone IIA (Tan IIA) is an active ingredient extracted from the widely used Danshen root (Salvia miltiorrhiza Bunge), a traditional Chinese medicine. Recent studies have indicated that Tan IIA may play important roles in anticancer treatment. However, its effects on the most common primary malignant bone tumor, osteosarcoma (OS), are unknown. Here, we report that Tan IIA may be an efficacious anti-OS drug as it could induce cell apoptosis and inhibit proliferation, migration, and invasion in vitro. Furthermore, we detected possible molecular mechanisms for Tan IIA activity by examining the levels of Bcl-2, Bax expression, and caspase-3, caspase-8, and caspase-9 activities that regulate apoptosis, matrix metalloproteinase (MMP)-2, and MMP-9 involved in regulating migration and invasion. In this study, we find that Tan IIA inhibits proliferation and induces apoptosis in the human OS cell line MG-63 in a time-dependent and dose-dependent manner. In addition, Tan IIA displays inhibitory activity on OS cell migration and invasion. Mechanistic studies have shown that Tan IIA activity is mediated by caspase activation. Tan IIA was also shown to reduce antiapoptotic Bcl-2, MMP-2, and MMP-9 levels, whereas it increased proapoptotic Bax levels. These data suggest that Tan IIA may be a novel, efficient candidate agent for OS treatment.
丹参酮 IIA(Tan IIA)是一种从广泛使用的丹参根(丹参)中提取的有效成分,丹参是一种传统的中药。最近的研究表明,Tan IIA 可能在癌症治疗中发挥重要作用。然而,它对最常见的原发性恶性骨肿瘤骨肉瘤(OS)的影响尚不清楚。在这里,我们报告 Tan IIA 可能是一种有效的抗 OS 药物,因为它可以在体外诱导细胞凋亡并抑制增殖、迁移和侵袭。此外,我们通过检查凋亡调节因子 Bcl-2、Bax 表达以及 caspase-3、caspase-8 和 caspase-9 活性,检测了 Tan IIA 活性的可能分子机制,这些因子调节细胞凋亡,基质金属蛋白酶(MMP)-2 和 MMP-9 参与调节迁移和侵袭。在这项研究中,我们发现 Tan IIA 以时间和剂量依赖的方式抑制人骨肉瘤细胞系 MG-63 的增殖并诱导其凋亡。此外,Tan IIA 对 OS 细胞迁移和侵袭具有抑制活性。机制研究表明,Tan IIA 的活性是通过半胱天冬酶的激活介导的。Tan IIA 还降低了抗凋亡的 Bcl-2、MMP-2 和 MMP-9 水平,而增加了促凋亡的 Bax 水平。这些数据表明,Tan IIA 可能是一种治疗骨肉瘤的新型、高效候选药物。