PMID- 19294695 OWN - NLM STAT- MEDLINE DCOM- 20090818 LR - 20181201 IS - 1615-9861 (Electronic) IS - 1615-9853 (Linking) VI - 9 IP - 7 DP - 2009 Apr TI - Synergistic effect of trichostatin A and 5-aza-2'-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: a proteomic study. PG - 1952-66 LID - 10.1002/pmic.200701089 [doi] AB - Our research group recently reported that pancreatic endocrine cancer cell lines are sensitive to the HDAC inhibitor trichostatin A (TSA). In the present paper, we show that the combined treatment of pancreatic endocrine tumour cell lines with TSA and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) determines a strong synergistic inhibition of proliferation mainly due to apoptotic cell death. Proteomic analysis demonstrates that the modulation of specific proteins correlates with the antiproliferative effect of the drugs. A schematic network clarifies the most important targets or pathways involved in pancreatic endocrine cancer growth inhibition by single or combined drug treatments, which include proteasome, mitochondrial apoptotic pathway and caspase related proteins, p53 and Ras related proteins. A comparison between the patterns of proteins regulated by TSA or DAC in endocrine and ductal pancreatic cancer cell lines is also presented. FAU - Cecconi, Daniela AU - Cecconi D AD - Dipartimento di Biotecnologie, Laboratorio di Proteomica, Universita di Verona, Verona, Italy. FAU - Donadelli, Massimo AU - Donadelli M FAU - Dalla Pozza, Elisa AU - Dalla Pozza E FAU - Rinalducci, Sara AU - Rinalducci S FAU - Zolla, Lello AU - Zolla L FAU - Scupoli, Maria Teresa AU - Scupoli MT FAU - Righetti, Pier Giorgio AU - Righetti PG FAU - Scarpa, Aldo AU - Scarpa A FAU - Palmieri, Marta AU - Palmieri M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Proteomics JT - Proteomics JID - 101092707 RN - 0 (Enzyme Inhibitors) RN - 0 (Hydroxamic Acids) RN - 3X2S926L3Z (trichostatin A) RN - 776B62CQ27 (Decitabine) RN - M801H13NRU (Azacitidine) SB - IM MH - Analysis of Variance MH - Apoptosis/drug effects MH - Azacitidine/*analogs & derivatives/pharmacology MH - Carcinoma, Pancreatic Ductal/metabolism MH - Cell Cycle MH - Cell Line, Tumor MH - Cell Proliferation/*drug effects MH - Decitabine MH - Drug Synergism MH - Endocrine Gland Neoplasms/metabolism MH - Enzyme Inhibitors/*pharmacology MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - Hydroxamic Acids/*pharmacology MH - Pancreatic Neoplasms/*metabolism EDAT- 2009/03/19 09:00 MHDA- 2009/08/19 09:00 CRDT- 2009/03/19 09:00 PHST- 2009/03/19 09:00 [entrez] PHST- 2009/03/19 09:00 [pubmed] PHST- 2009/08/19 09:00 [medline] AID - 10.1002/pmic.200701089 [doi] PST - ppublish SO - Proteomics. 2009 Apr;9(7):1952-66. doi: 10.1002/pmic.200701089.