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脱水穿心莲内酯通过靶向 SATB2 介导的 EMT 抑制骨肉瘤细胞生长和转移。

Dehydroandrographolide Inhibits Osteosarcoma Cell Growth and Metastasis by Targeting SATB2-mediated EMT.

机构信息

Department of Forensic Pathology, Xi'an Jiaotong University, School of Medicine, Xi'an, 710061, China.

Department of Anatomy, Jinzhou Medical University, Jinzhou, 121001, China.

出版信息

Anticancer Agents Med Chem. 2019;19(14):1728-1736. doi: 10.2174/1871520619666190705121614.

DOI:10.2174/1871520619666190705121614
PMID:31284872
Abstract

BACKGROUND

The 12-hydroxy-14-dehydroandrographolide (DP) is a predominant component of the traditional herbal medicine (Burm. f.) Nees (Acanthaceae). Recent studies have shown that DP exhibits potent anti-cancer effects against oral and colon cancer cells.

OBJECTIVE

This investigation examined the potential effects of DP against osteosarcoma cell.

METHODS

A cell analyzer was used to measure cell viability. The cell growth and proliferation were performed by Flow cytometry and BrdU incorporation assay. The cell migration and invasion were determined by wound healing and transwell assay. The expression of EMT related proteins was examined by Western blot analysis.

RESULTS

In this study, we found that DP treatment repressed osteosarcoma (OS) cell growth in a dose-dependent manner. DP treatment significantly inhibited OS cell proliferation by arresting the cell cycle at G2/M phase. In addition, DP treatment effectively inhibited the migration and invasion abilities of OS cells through wound healing and Transwell tests. Mechanistic studies revealed that DP treatment effectively rescued the epithelialmesenchymal transition (EMT), while forced expression of SATB2 in OS cells markedly reversed the pharmacological effect of DP on EMT.

CONCLUSION

Our data demonstrated that DP repressed OS cell growth through inhibition of proliferation and cell cycle arrest; DP also inhibited metastatic capability of OS cells through a reversal of EMT by targeting SATB2. These findings demonstrate DP's potential as a therapeutic drug for OS treatment.

摘要

背景

12-羟基-14-去氢穿心莲内酯(DP)是传统草药(穿心莲)(爵床科)的主要成分。最近的研究表明 DP 对口腔和结肠癌细胞具有很强的抗癌作用。

目的

本研究考察 DP 对骨肉瘤细胞的潜在作用。

方法

细胞分析仪用于测量细胞活力。通过流式细胞术和 BrdU 掺入试验检测细胞生长和增殖。通过划痕愈合和 Transwell 试验测定细胞迁移和侵袭。通过 Western blot 分析检测 EMT 相关蛋白的表达。

结果

在这项研究中,我们发现 DP 处理以剂量依赖的方式抑制骨肉瘤(OS)细胞生长。DP 处理通过将细胞周期阻滞在 G2/M 期显著抑制 OS 细胞增殖。此外,DP 处理通过划痕愈合和 Transwell 试验有效抑制 OS 细胞的迁移和侵袭能力。机制研究表明,DP 处理通过 EMT 有效挽救上皮-间充质转化(EMT),而在 OS 细胞中强制表达 SATB2 则明显逆转 DP 对 EMT 的药理学作用。

结论

我们的数据表明 DP 通过抑制增殖和细胞周期阻滞抑制 OS 细胞生长; DP 还通过靶向 SATB2 逆转 EMT 来抑制 OS 细胞的转移能力。这些发现表明 DP 具有作为骨肉瘤治疗药物的潜力。

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