Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy.
Department of Sciences and Technological Innovation, University of Piemonte Orientale, Alessandria, Italy.
J Cell Biochem. 2018 Mar;119(3):2696-2707. doi: 10.1002/jcb.26436. Epub 2017 Nov 21.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal of all human cancers with a high mortality rate. Resistance to conventional treatments and chemotherapeutics is a typical feature of PDAC. To investigate the causes of drug resistance it is essential to deeply investigate the mechanism of action of chemotherapeutics. In this study, we performed an in depth shotgun proteomic approach using the label-free proteomic SWATH-MS analysis to investigate novel insights of the mechanism of action of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) in PDAC cells. This proteomic analysis in PaCa44 cells and data elaboration of TSA-regulated proteins by bioinformatics showed an overall up-regulation of cytokeratins and other proteins related to the cytoskeleton organization, keratinization, and apoptotic cell death. On the contrary, a large amount of the down-regulated proteins by TSA treatment belongs to the cellular energetic metabolism and to the machinery of protein synthesis, such as ribosomal proteins, determining synergistic cell growth inhibition by the combined treatment of TSA and the glycolytic inhibitor 2-deoxy-d-glucose in a panel of PDAC cell lines. Data are available via ProteomeXchange with identifier PXD007801.
胰腺导管腺癌（PDAC）是人类所有癌症中最致命的癌症之一，死亡率很高。对常规治疗和化疗药物的耐药性是 PDAC 的一个典型特征。为了研究耐药的原因，深入研究化疗药物的作用机制至关重要。在这项研究中，我们使用无标记蛋白质组学 SWATH-MS 分析进行了深入的鸟枪法蛋白质组学研究，以研究组蛋白去乙酰化酶（HDAC）抑制剂曲古抑菌素 A（TSA）在 PDAC 细胞中的作用机制的新见解。这项在 PaCa44 细胞中的蛋白质组学分析和通过生物信息学对 TSA 调节蛋白的数据阐述表明，细胞角蛋白和其他与细胞骨架组织、角化和细胞凋亡相关的蛋白质总体上调。相反，TSA 处理下调的大量蛋白质属于细胞能量代谢和蛋白质合成机制，如核糖体蛋白，这决定了 TSA 和糖酵解抑制剂 2-脱氧-D-葡萄糖在一系列 PDAC 细胞系中的联合处理的协同细胞生长抑制作用。数据可通过 ProteomeXchange 以标识符 PXD007801 获得。
