Antitumor Activity of Histone Deacetylase Inhibitor Trichostatin A in Osteosarcoma Cells
Antitumor Activity of Histone Deacetylase Inhibitor Trichostatin A in Osteosarcoma Cells
复制标题
组蛋白脱乙酰酶抑制剂曲古抑菌素 A 在骨肉瘤细胞中的抗肿瘤活性。
DOI：
10.7314/apjcp.2012.13.4.1395
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Liu, Yi-Wen
中科院分区：
文献类型：
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作者：
Cheng, Dong-Dong;Yang, Qing-Cheng;Liu, Yi-Wen
背景：组蛋白去乙酰化酶（HDAC）抑制剂可诱导肿瘤细胞生长停滞、凋亡和分化。本研究旨在探讨骨肉瘤抑制剂甲素（TSA）对骨肉瘤细胞周期、凋亡和侵袭力的影响。方法：用不同浓度TSA处理MG-63细胞。MTT法检测细胞生长，TUNEL法检测细胞凋亡，流式细胞仪检测细胞周期，transwell Boyden小室检测细胞侵袭能力。结果：MTT法显示TSA对MG-63细胞的生长有明显的抑制作用，并呈浓度和时间依赖性。TSA处理的细胞表现出凋亡的形态学变化，TUNEL检测显示TSA处理后MG-63细胞的凋亡增加。流式细胞仪显示TSA使细胞周期阻滞于G1/G2期，Annexin V阳性凋亡细胞明显增多。TSA对MG-63细胞的侵袭能力有明显的抑制作用，且呈浓度依赖性。结论：TSA在体外可抑制骨肉瘤细胞的增殖、诱导凋亡和抑制侵袭力。因此，HDAC抑制剂有望成为新的骨肉瘤治疗药物。
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.