title: Viability of D283 medulloblastoma cells treated with a histone deacetylase inhibitor combined with bombesin receptor antagonists.
abstract: OBJECTIVE
  Medulloblastoma (MB) comprises four distinct molecular subgroups, and survival remains particularly poor in patients with Group 3 tumors. Mutations and copy number variations result in altered epigenetic regulation of gene expression in Group 3 MB. Histone deacetylase inhibitors (HDACi) reduce proliferation, promote cell death and neuronal differentiation, and increase sensitivity to radiation and chemotherapy in experimental MB. Bombesin receptor antagonists potentiate the antiproliferative effects of HDACi in lung cancer cells and show promise as experimental therapies for several human cancers. Here, we examined the viability of D283 cells, which belong to Group 3 MB, treated with an HDACi alone or combined with bombesin receptor antagonists.
  
  
  METHODS
  D283 MB cells were treated with different doses of the HDACi sodium butyrate (NaB), the neuromedin B receptor (NMBR) antagonist BIM-23127, the gastrin releasing peptide receptor (GRPR) antagonist RC-3095, or combinations of NaB with each receptor antagonist. Cell viability was examined by cell counting.
  
  
  RESULTS
  NaB alone or combined with receptor antagonists reduced cell viability at all doses tested. BIM-23127 alone did not affect cell viability, whereas RC-3095 at an intermediate dose significantly increased cell number.
  
  
  CONCLUSIONS
  Although HDACi are promising agents to inhibit MB growth, the present results provide preliminary evidence that combining HDACi with bombesin receptor antagonists is not an effective strategy to improve the effects of HDACi against MB cells.
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Mariane
authors.initials: M
authors.lastname: Jaeger
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Eduarda C
authors.initials: EC
authors.lastname: Ghisleni
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Lívia
authors.initials: L
authors.lastname: Fratini
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.|Children's Cancer Institute (ICI), Porto Alegre, RS, Brazil.
authors.forename: Algemir L
authors.initials: AL
authors.lastname: Brunetto
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Lauro José
authors.initials: LJ
authors.lastname: Gregianin
authors.affiliation: Children's Cancer Institute (ICI), Porto Alegre, RS, Brazil.
authors.forename: André T
authors.initials: AT
authors.lastname: Brunetto
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.|Department of Internal Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.|Children's Cancer Institute (ICI), Porto Alegre, RS, Brazil.
authors.forename: Caroline B
authors.initials: CB
authors.lastname: de Farias
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. rroesler@terra.com.br.|Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), Porto Alegre, RS, 90050-170, Brazil. rroesler@terra.com.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
mesh_terms: D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008527:Medulloblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C092829:BIM 23127; D056572:Histone Deacetylase Inhibitors; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018004:Receptors, Bombesin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D001839:Bombesin
keywords: Brain tumor; Gastrin-releasing peptide receptor; Neuromedin B receptor; Sodium butyrate