Proteomic analysis of pancreatic endocrine tumor cell lines treated with the histone deacetylase inhibitor trichostatin A
Proteomic analysis of pancreatic endocrine tumor cell lines treated with the histone deacetylase inhibitor trichostatin A
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DOI：
10.1002/pmic.200600811
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发表时间：
2007-05-01
期刊：
影响因子：
3.4
通讯作者：
Righetti, Pier Giorgio
中科院分区：
文献类型：
--
作者：
Cecconi, Daniela;Donadelli, Massimo;Righetti, Pier Giorgio
通过剂量依赖性生长抑制曲线评估组蛋白去乙酰化酶抑制剂曲古抑素A （trichostatin A， TSA）对三种不同人胰腺内分泌癌细胞（CM、BON和QGP-1）生长的影响。TSA通过抑制G2/M期细胞周期并诱导细胞凋亡，对不同细胞系80.5 nM （CM）、61.6 nM （BON）和86 nM （QGP-1）的细胞生长具有较强的抑制作用，IC50值相近。2DE和纳米rp - hplc - esi -MS/MS分析显示，经TSA处理后，CM、BON和QGP-1细胞系中分别有34、33和38个独特的蛋白差异表达。最重要的调节蛋白群属于细胞增殖、细胞周期和细胞凋亡类（如过氧化物还毒素1和2、diablo蛋白和HSP27）。其他蛋白质与基因表达（核磷蛋白、癌蛋白dek）、信号转导（钙钙调素）、染色质和细胞骨架组织（钙蛋白、动力蛋白和层粘连蛋白）、RNA剪接（核仁蛋白、HNRPC）和蛋白质折叠（HSP70）等过程有关。目前的数据与先前对胰腺导管癌细胞系进行的蛋白质组学分析一致（Cecconi， D. et al.，电泳2003；Cecconi， D. et al.， J. Proteome Res. 2005），并将组蛋白去乙酰化酶抑制剂列为治疗胰腺肿瘤的潜在最有效药物之一。
Effects of the histone-deacetylases inhibitor trichostatin A (TSA) on the growth of three different human pancreatic endocrine carcinoma cell lines (CM, BON, and QGP-1) have been assessed via dosage-dependent growth inhibition curves. TSA determined strong inhibition of cell growth with similar IC50 values for the different cell lines: 80.5 nM (CM), 61.6 nM (BON), and 86 nM (QGP-1), by arresting the cell cycle in G2/M phase and inducing apoptosis. 2DE and nano-RP-HPLC-ESI-MS/MS analysis revealed 34, 33, and 38 unique proteins differentially expressed after TSA treatment in the CM, BON, and QGP-1 cell lines, respectively. The most important groups of modulated proteins belong to cell proliferation, cell cycle, and apoptosis classes (such as peroxiredoxins 1 and 2, the diablo protein, and HSP27). Other proteins pertain to processes such as regulation of gene expression (nucleophosmin, oncoprotein dek), signal transduction (calcium-calmodulin), chromatin, and cytoskeleton organization (calgizzarin, dynein, and lamin), RNA splicing (nucleolin, HNRPC), and protein folding (HSP70). The present data are in agreement with previous proteomic analyses performed on pancreatic ductal carcinoma cell lines (Cecconi, D. et al., Electrophoresis 2003; Cecconi, D. et al., J. Proteome Res. 2005) and place histone-deacetylases inhibitors among the potentially most powerful drugs for the treatment of pancreatic tumors.