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丹参酮 IIA 诱导骨肉瘤 MG-63 细胞系凋亡并抑制其体外增殖、迁移和侵袭。

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

机构信息

Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.

出版信息

Anticancer Drugs. 2012 Feb;23(2):212-9. doi: 10.1097/CAD.0b013e32834e5592.

DOI:10.1097/CAD.0b013e32834e5592
PMID:22126901
Abstract

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.

摘要

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。

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Tanshinone IIA induces apoptosis and inhibits the proliferation, migration, and invasion of the osteosarcoma MG-63 cell line in vitro.丹参酮 IIA 诱导骨肉瘤 MG-63 细胞系凋亡并抑制其体外增殖、迁移和侵袭。
Anticancer Drugs. 2012 Feb;23(2):212-9. doi: 10.1097/CAD.0b013e32834e5592.
2
Tanshinone IIA inhibits Hep-J5 cells by increasing calreticulin, caspase 12 and GADD153 protein expression.丹参酮 IIA 通过增加钙网织蛋白、半胱天冬酶 12 和 GADD153 蛋白的表达来抑制 Hep-J5 细胞。
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Tanshinone IIA inhibits BT-20 human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression.丹参酮 IIA 通过增加半胱天冬酶 12、GADD153 和磷酸化 p38 蛋白的表达抑制 BT-20 人乳腺癌细胞增殖。
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Anti-angiogenic effect of Tanshinone IIA involves inhibition of matrix invasion and modification of MMP-2/TIMP-2 secretion in vascular endothelial cells.丹参酮 IIA 的抗血管生成作用涉及抑制基质浸润和改变血管内皮细胞中 MMP-2/TIMP-2 的分泌。
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Tanshinone IIA inhibits constitutive STAT3 activation, suppresses proliferation, and induces apoptosis in rat C6 glioma cells.丹参酮 IIA 抑制组成性 STAT3 激活,抑制增殖,并诱导大鼠 C6 神经胶质瘤细胞凋亡。
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Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction.丹参酮 IIA 诱导骨肉瘤细胞在体内在体外发生内在凋亡,并与线粒体功能障碍有关。
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Tanshinone IIA reduces apoptosis induced by hydrogen peroxide in the human endothelium-derived EA.hy926 cells.丹参酮 IIA 可减少人内皮细胞源性 EA.hy926 细胞过氧化氢诱导的细胞凋亡。
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Tanshinone IIA inhibits human prostate cancer cells growth by induction of endoplasmic reticulum stress in vitro and in vivo.丹参酮 IIA 通过诱导内质网应激在体外和体内抑制人前列腺癌细胞生长。
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Sodium Tanshinone IIA Sulfonate Attenuates Tumor Oxidative Stress and Promotes Apoptosis in an Intermittent Hypoxia Mouse Model.丹参酮 IIA 磺酸钠减轻间歇性低氧小鼠模型肿瘤氧化应激并促进细胞凋亡。
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