Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.
Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.
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DOI：
10.3892/ijmm.2012.1192
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发表时间：
2013
影响因子：
5.4
通讯作者：
Zeng-Feng Xin;Cheng-chun Shen;Li-jiang Tao;Shi-gui Yan;Hao-bo Wu
中科院分区：
文献类型：
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作者：
Zeng-Feng Xin;Cheng-chun Shen;Li-jiang Tao;Shi-gui Yan;Hao-bo Wu
藤黄酸（GA）是一种天然产物，由于其诱导细胞凋亡和细胞周期停滞的能力，已被证明是一种有前途的骨肉瘤（OS）化疗药物。迄今为止，还没有研究探讨 GA 在转移性骨疾病中的作用。基质金属蛋白酶（MMP）在侵袭和转移中发挥关键作用，金属蛋白酶组织抑制剂（TIMP）家族调节多功能金属蛋白酶的活性。在本研究中，我们研究了 GA 处理的 OS 细胞系中基质金属蛋白酶 9 (MMP-9) 和基质金属蛋白酶组织抑制剂 - 1 (TIMP-1) 的基因表达。通过逆转录聚合酶链反应（RT-PCR）和蛋白质印迹研究MMP-9和TIMP-1的表达。通过 Matrigel 侵袭试验研究 OS 细胞系（Saos-2、MG-63）的体外侵袭。平均MMP-9蛋白和mRNA表达显着受到抑制；此外，平均 TIMP-1 蛋白 mRNA 表达随着 GA 浓度的增加而上调。 GA 剂量依赖性地降低 OS 细胞系的侵袭性。此外，用针对TIMP-1的siRNA特异性抑制TIMP-1分泌显着降低了GA对OS细胞系的影响。总的来说，我们的研究结果表明，GA 通过减弱 MMP-9 和上调 TIMP-1 来降低 OS 细胞的侵袭潜力。此外，TIMP-1在降低经GA处理的OS细胞的侵袭能力方面发挥着重要作用。
Gambogic acid (GA), the natural product, has been demonstrated to be a promising chemotherapeutic drug for osteosarcoma (OS) due to its ability to induce apoptosis and cell cycle arrest. To date, no studies have examined the role of GA in metastatic bone disease. Matrix metalloproteinases (MMPs) play critical roles in invasion and metastasis, and the tissue inhibitors of metalloproteinase (TIMP) family regulates the activity of multifunctional metalloproteinases. In this study, we investigated the gene expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in OS cell lines treated by the GA. The expression of MMP-9 and TIMP-1 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. In vitro invasion of OS cell lines (Saos-2, MG-63) were investigated by the Matrigel invasion assay. Mean MMP-9 protein and mRNA expression was significantly suppressed; in addition, mean TIMP-1 protein mRNA expression were upregulated by increasing GA concentrations. GA reduced the invasiveness of OS cell lines dose-dependently. Furthermore, specific inhibition of TIMP-1 secretion with siRNA against TIMP-1 significantly reduced the effect of GA on OS cell lines. Overall, our findings suggest that GA reduces the invasive potential of OS cells via attenuation of MMP-9 and upregulation of TIMP-1. Moreover, TIMP-1 played an important role in the reduction of invasive potential of the OS cells which were treated by GA.