Tanshinone IIA induces apoptosis and inhibits the proliferation, migration, and invasion of the osteosarcoma MG-63 cell line in vitro

Tanshinone IIA induces apoptosis and inhibits the proliferation, migration, and invasion of the osteosarcoma MG-63 cell line in vitro
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DOI:
10.1097/cad.0b013e32834e5592
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发表时间:
2012-02
期刊:
影响因子:
2.3
通讯作者:
Yi Zhang;Ren-xiong Wei;Xiaobao Zhu;Lin Cai;Wei Jin;Hao Hu
Yi Zhang;Ren-xiong Wei;Xiaobao Zhu;Lin Cai;Wei Jin;Hao Hu
中科院分区:
医学4区
文献类型:
--
作者:
Yi Zhang;Ren-xiong Wei;Xiaobao Zhu;Lin Cai;Wei Jin;Hao Hu

文献摘要

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丹参酮IIA(Tanshinone IIA)是从传统中药丹参(Salvia miltiorrhiza Bunge)中提取的有效成分。最近的研究表明,Tan IIA可能在抗癌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。在此,我们报道Tan IIA可能是一种有效的抗OS药物,因为它可以诱导细胞凋亡,并抑制体外增殖、迁移和侵袭。此外,我们通过检测Bcl-2、Bax表达水平,以及调节凋亡的caspase-3、caspase-8和caspase-9活性,以及参与调节迁移和侵袭的基质金属蛋白酶(MMP)-2和MMP-9,来检测Tan IIA活性的可能分子机制。在本研究中,我们发现Tan IIA以时间依赖和剂量依赖的方式抑制人OS细胞系MG-63的增殖并诱导其凋亡。此外,Tan IIA对OS细胞迁移和侵袭显示抑制活性。机制研究表明,Tan IIA活性是由caspase激活介导的。Tan IIA还显示降低抗凋亡Bcl-2、MMP-2和MMP-9水平,而增加促凋亡Bax水平。这些数据表明,谭IIA可能是一种新的,有效的候选药物治疗OS。
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.