Viability of D283 medulloblastoma cells treated with a histone deacetylase inhibitor combined with bombesin receptor antagonists

• Published in: Child's nervous system Vol. 32; no. 1; pp. 61 - 64
• Main Authors: Jaeger, Mariane, Ghisleni, Eduarda C., Fratini, Lívia, Brunetto, Algemir L., Gregianin, Lauro José, Brunetto, André T., Schwartsmann, Gilberto, de Farias, Caroline B., Roesler, Rafael
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2016
• Subjects: Analysis of Variance; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Bombesin - analogs & derivatives; Bombesin - pharmacology; Brief Communication; Cell Line, Tumor; Cell Survival - drug effects; Dose-Response Relationship, Drug; Histone Deacetylase Inhibitors - pharmacology; Humans; Medicine; Medicine & Public Health; Medulloblastoma - pathology; Neurosciences; Neurosurgery; Peptide Fragments - pharmacology; Peptides, Cyclic - pharmacology; Receptors, Bombesin - antagonists & inhibitors; Brain tumor; Neuromedin B receptor; Sodium butyrate; Gastrin-releasing peptide receptor
• ISSN: 0256-7040; 1433-0350
• DOI: 10.1007/s00381-015-2963-4

Purpose 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. Conclusion 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.