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组蛋白去乙酰化酶抑制剂曲古抑菌素A在骨肉瘤细胞中的抗肿瘤活性

Antitumor activity of histone deacetylase inhibitor trichostatin A in osteosarcoma cells.

作者信息

Cheng Dong-Dong, Yang Qing-Cheng, Zhang Zhi-Chang, Yang Cui-Xia, Liu Yi-Wen

机构信息

Department of Orthopeadics, Sixth People's Hospital, Shanghai JiaoTong University, Shanghai, China.

出版信息

Asian Pac J Cancer Prev. 2012;13(4):1395-9. doi: 10.7314/apjcp.2012.13.4.1395.

Abstract

BACKGROUND

Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation of tumor cells. The present study aimed to examine the effects of trichostatin A (TSA), one such inhibitor, on the cell cycle, apoptosis and invasiveness of osteosarcoma cells.

METHODS

MG- 63 cells were treated with TSA at various concentrations. Then, cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively; cell cycling was assessed by flow cytometry; invasion assays were performed with the transwell Boyden Chamber system.

RESULTS

MTT assays revealed that TSA significantly inhibited the growth of MG-63 cells in a concentration and time dependent manner. TSA treated cells demonstrated morphological changes indicative of apoptosis and TUNEL assays revealed increased apoptosis of MG-63 cells after TSA treatment. Flow cytometry showed that TSA arrested the cell cycle in G1/G2 phase and annexin V positive apoptotic cells increased markedly. In addition, the invasiveness of MG-63 cells was inhibited by TSA in a concentration dependent manner.

CONCLUSION

Our findings demonstrate that TSA inhibits the proliferation, induces apoptosis and inhibits invasiveness of osteosarcoma cells in vitro. HDAC inhibitors may thus have promise to become new therapeutic agents against osteosarcoma.

摘要

背景

据报道,组蛋白脱乙酰酶(HDAC)抑制剂可诱导肿瘤细胞的生长停滞、凋亡和分化。本研究旨在检测曲古抑菌素A(TSA)这种抑制剂对骨肉瘤细胞的细胞周期、凋亡和侵袭性的影响。

方法

用不同浓度的TSA处理MG-63细胞。然后,分别通过3-(4,5-二甲基-2-噻唑基)-2H-四唑溴盐(MTT)法和TUNEL法检测细胞生长和凋亡;通过流式细胞术评估细胞周期;用Transwell Boyden小室系统进行侵袭实验。

结果

MTT实验显示,TSA以浓度和时间依赖性方式显著抑制MG-63细胞的生长。经TSA处理的细胞表现出指示凋亡的形态学变化,TUNEL实验显示TSA处理后MG-63细胞的凋亡增加。流式细胞术表明,TSA使细胞周期停滞在G1/G2期,膜联蛋白V阳性凋亡细胞显著增加。此外,TSA以浓度依赖性方式抑制MG-63细胞的侵袭性。

结论

我们的研究结果表明,TSA在体外抑制骨肉瘤细胞的增殖,诱导凋亡并抑制其侵袭性。因此,HDAC抑制剂有望成为抗骨肉瘤的新型治疗药物。

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