丁凡;邵增务;

• 1:华中科技大学同济医学院附属协和医院骨科

摘要(Abstract)：

[目的]观察组蛋白去乙酰化酶抑制剂曲古抑菌素A(TSA)对人骨肉瘤MG-63细胞增殖和分化的影响。[方法]不同浓度的TSA作用MG-63细胞,采用噻唑蓝(MTT)法、倒置相差显微镜观察药物对细胞生长的影响并绘制细胞生长曲线;软琼脂集落形成实验观察细胞生长和侵袭能力的变化;流式细胞仪测定细胞周期变化。[结果]TSA可明显抑制MG-63细胞增殖,并呈现剂量和时间的依赖性;细胞形态呈明显的良性分化;瘤细胞的软琼脂集落形成率明显降低;TSA能够延缓细胞周期G1-S进程,阻滞细胞于G1期,停留在G2/M期。[结论]TSA对MG-63细胞有明显的抑制增殖和诱导分化作用。

关键词(KeyWords)： 骨肉瘤;组蛋白去乙酰化酶;曲古抑菌素A;分化

Abstract:

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作者(Author): 丁凡;邵增务;

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参考文献(References)：

• [1]Lachner M,O'Carroll D,Rea S,et al.Methylation of histoneH3lysine9creates a binding site for HP1proteins[J].Nature,2001,410:116-120.
• [2]Tom H,Peggy P,Greetje E,et al.Trichostatin A,a critical factor in maintaining the functional differentiation of primary cultured rat hepa-tocytes[J].Toxicol App Pharmacol,2007,218:64-71.
• [3]Jyothsna R,Dipanjan B,Bidisha B,et al.Trichostatin-A induces dif-ferential changes in histone protein dynamics and expression in HeLa cells[J].Biochem Biophys Res Commun,2007,363:263-268.
• [4]高建强,陈方方,张嵩,等.去甲基化和组蛋白去乙酰化转移酶抑制剂对Ishikawa和AN3细胞增殖的凋亡的影响[J].中华肿瘤防治杂志,2007,9:666-669.
• [5]Nicole S,Sabine S,Careen K,et al.The histone deacetylase inhibitor trichostatin A mediates upregulation of5-lipoxygenase promoter ac-tivity by recruitment of Sp1to distinct GC-boxes[J].Biochem Bio-phys Acta,2007,1771:1271-1282.
• [6]Mohsen H,Koji H,Koh O,et al.Trichostatin A induces myocardial differentiation of monkey ES cells[J].Biochem Biophys Res Com-mun,2007,356:386-391.
• [7]Jing-Ni O,Je rome T,Alexander U,et al.Histone deacetylase inhib-itor trichostatin A induces global and gene-specific DNA demethyla-tion in human cancer cell lines[J].Biochem Pharmacol,2007,73:1297-1307.
• [8]Piotrowska H,Jagodzinski PP.Trichostatin A,sodium butyrate,and5-aza-2-deoxycytidine alter the expression of glucocorticoid recep-tor a and b isoforms in Hut-78T-and Raji B-lymphoma cell lines[J].Biomed Pharmacother,2007,61:451-454.
• [9]Eunjin K,Russell B,Timothy C,et al.Trichostatin Aand5-aza-2-deoxycytidine switch S1P from an inhibitor to a stimulator of motili-ty through epigenetic regulation of S1P receptors[J].Cancer Lett,2007,250:53-62.
• [10]Tom H,Peggy P,Greetje E,et al.Trichostatin A,a critical factor in maintaining the functional differentiation of primary cultured rat hepa-tocytes[J].Toxicol Appl Pharmacol,2007,218:64-71.
• [11]Studzinski GP,Harrison LE.Diifferentiation-related changes in the cell traverse[J].Int Rev Cytol,1999,10:1-58.
• [12]雷振东,彭聪,赵华,等.曲骨抑菌素A对结肠癌细胞株SW480细胞周期影响的机制研究[J].生命科学研究,2006,1:39-44.
• [13]丁凡,邵增务.骨肉瘤基因治疗研究进展[J].中国矫形外科杂志,2008,16:1326-1328.