ONTOLOGY SOURCE REFERENCE Term Source Name "ArrayExpress" "EFO" "NCBITaxon" "MSH" "BTO" "CHEBI" "XCO" "" "OBI" Term Source File "http://www.ebi.ac.uk/arrayexpress/" "http://www.ebi.ac.uk/efo/efo.owl" "http://bioportal.bioontology.org/ontologies/47845" "http://bioportal.bioontology.org/ontologies/46836" "http://bioportal.bioontology.org/ontologies/50688" "http://bioportal.bioontology.org/ontologies/50716" "http://bioportal.bioontology.org/ontologies/50737" "" "" Term Source Version "" "" "47845" "46836" "50688" "50716" "50737" "" "" Term Source Description "" "" "National Center for Biotechnology Information (NCBI) Organismal Classification" "Medical Subject Headings" "BRENDA Tissue and Enzyme Source Ontology" "Chemical Entities of Biological Interest Ontology" "Experimental Conditions Ontology" "" "" INVESTIGATION Investigation Identifier "" Investigation Title "" Investigation Description "" Investigation Submission Date "" Investigation Public Release Date "" Comment [Created with configuration] "" Comment [Last Opened With Configuration] "" INVESTIGATION PUBLICATIONS Investigation PubMed ID "" Investigation Publication DOI "" Investigation Publication Author List "" Investigation Publication Title "" Investigation Publication Status "" Investigation Publication Status Term Accession Number "" Investigation Publication Status Term Source REF "" INVESTIGATION CONTACTS Investigation Person Last Name "" Investigation Person First Name "" Investigation Person Mid Initials "" Investigation Person Email "" Investigation Person Phone "" Investigation Person Fax "" Investigation Person Address "" Investigation Person Affiliation "" Investigation Person Roles "" Investigation Person Roles Term Accession Number "" Investigation Person Roles Term Source REF "" STUDY Study Identifier "E-GEOD-45340" Study Title "Combination of celecoxib and sorafenib provides synergistic antiproliferative and proapoptotic effects in human liver cancer cells" Study Description "Transcriptional profiling of HepG2 and Huh7 cells treated with celecoxib plus the kinase inhibitor sorafenib. [original description: Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of combination, we investigated the expression profile of the combination-treated liver cancer cell lines, using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes, functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell line displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semiquantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomics analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies. To identify new potential mechanisms of combined action of celecoxib and sorafenib, their effects on global gene expression in both cell lines were investigated and compared using the DNA microarray technology. Agilent 44K Human Whole Genome Oligonucleotide Microarrays (containing ~44,000 genes) were used to identify global gene expression changes in the HepG2 and Huh7 hepatocellular carcinoma (HCC) cell lines, following simultaneous treatment with 50 µM celecoxib and 7.5 µM sorafenib for 48 hours. All microarray experiments (a total of four) were performed in duplicates applying dye-swaps to avoid labeling bias.]" Comment[Study Grant Number] "" Comment[Study Funding Agency] "" Study Submission Date "" Study Public Release Date "2013-03-21" Study File Name "s_E-GEOD-45340_study_samples.txt" STUDY DESIGN DESCRIPTORS Study Design Type "transcription profiling by array" Study Design Type Term Accession Number "" Study Design Type Term Source REF "" STUDY PUBLICATIONS Study PubMed ID "23776502" Study Publication DOI "10.1371/journal.pone.0065569" Study Publication Author List "Cervello M, Bachvarov D, Lampiasi N, Cusimano A, Azzolina A, McCubrey JA, Montalto G." Study Publication Title "Novel combination of sorafenib and celecoxib provides synergistic anti-proliferative and pro-apoptotic effects in human liver cancer cells." Study Publication Status "Published" Study Publication Status Term Accession Number "" Study Publication Status Term Source REF "" STUDY FACTORS Study Factor Name "cell line" "drug1" "drug2" Study Factor Type "cell line" "drug treatment" "drug treatment" Study Factor Type Term Accession Number "" "" "" Study Factor Type Term Source REF "" "" "" STUDY ASSAYS Study Assay File Name "a_E-GEOD-45340_GeneChip_assay.txt" Study Assay Measurement Type "transcription profiling" Study Assay Measurement Type Term Accession Number "" Study Assay Measurement Type Term Source REF "" Study Assay Technology Type "DNA microarray" Study Assay Technology Type Term Accession Number "" Study Assay Technology Type Term Source REF "" Study Assay Technology Platform "" STUDY PROTOCOLS Study Protocol Name "P-GSE45340-3" "P-GSE45340-2" "P-GSE45340-4" "P-GSE45340-5" "P-GSE45340-6" "P-GSE45340-7" "P-GSE45340-8" "P-GSE45340-1" Study Protocol Type "grow" "specified_biomaterial_action" "nucleic_acid_extraction" "labeling" "hybridization" "image_aquisition" "feature_extraction" "bioassay_data_transformation" Study Protocol Type Term Accession Number "" "" "" "" "" "" "" "" Study Protocol Type Term Source REF "" "" "" "" "" "" "" "" Study Protocol Description "HepG2 and Huh7 cells were maintained in Roswell Park Memorial Institute (RPMI) 1640 (HyClone Europe Ltd, Cramlington, UK) supplemented with 10% heat-inactivated fetal calf serum, 2 mM l-glutamine, 1 mM sodium pyruvate, 100 units/ml penicillin and 100 μg/ml streptomycin (all reagents were from HyClone Europe). Cells were grown as adherent cells in a humidified atmosphere at 37°C in 5% CO2. " "The human HCC cell lines HepG2 and Huh7 were treated simultaneously with 50 µM celecoxib and 7.5 µM sorafenib for 48 hours. " "Total RNA extracted using Trizol following manufacturer's instructions. The quality of all RNA samples was examined by capillary electrophoresis using the Agilent 2100 Bioanalyzer." "Fluorescently labeled cRNA targets were generated from 0.5 µg of total RNA in each reaction using the Fluorescent Linear Amplification Kit (Agilent) and 10.0 mM Cyanine 3- or 5-labeled CTP (PerkinElmer, Boston, MA), following the user’s manual. Labeled cRNAs were purified using the RNeasy Mini Kit (Qiagen) and applied to the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes." "Oligoarray control targets and hybridization buffer (Agilent In Situ Hybridization Kit Plus) were added, and samples were applied to microarrays enclosed in Agilent SureHyb-enabled hybridization chambers." "Scanned on an Agilent G2565AA scanner." "Agilent Feature Extraction Software (v 8.5.1.1) was used for background subtraction and LOWESS normalization." "ID_REF = VALUE = normalized log10 ratio (Cy5/Cy3)" Study Protocol URI "" "" "" "" "" "" "" "" Study Protocol Version "" "" "" "" "" "" "" "" Study Protocol Parameters Name "" "" "" "" "" "" "" "" Study Protocol Parameters Name Term Accession Number "" "" "" "" "" "" "" "" Study Protocol Parameters Name Term Source REF "" "" "" "" "" "" "" "" Study Protocol Components Name "" "" "" "" "" "" "" "" Study Protocol Components Type "" "" "" "" "" "" "" "" Study Protocol Components Type Term Accession Number "" "" "" "" "" "" "" "" Study Protocol Components Type Term Source REF "" "" "" "" "" "" "" "" STUDY CONTACTS Study Person Last Name "Bachvarov" "Bachvarov" Study Person First Name "Dimcho" "Dimcho" Study Person Mid Initials "" "" Study Person Email "dimtcho.batchvarov@crhdq.ulaval.ca" "" Study Person Phone "(418) 525-4444" "" Study Person Fax "(418) 691-5439" "" Study Person Address "Medicine, Laval university, 9, rue McMahon, Quebec, Quebec, Canada" "" Study Person Affiliation "Laval university" "" Study Person Roles "submitter" "" Study Person Roles Term Accession Number "" "" Study Person Roles Term Source REF "" "" Comment[Study Person REF] "" ""