Abstract | BACKGROUND & AIMS: METHODS: RESULTS: HDAC2 was expressed in human gastric cancer cell lines and tumor samples, as well as in gastric tumors from CEA/Tag mice, compared with non-neoplastic gastric tissue. LBH589 inhibited proliferation of cancer cells in vitro. LBH589 down-regulated expression of genes that mediate anthracycline resistance by activating expression of Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), a gene that mediates sensitivity to chemotherapeutics. Pre-incubation of cells with an HDAC inhibitor and overexpression of CITED2-sensitized gastric cell lines to anthracycline-mediated cell death. In CEA/Tag mice, LBH589 induced tumor-cell expression of CITED2 and increased the efficacy of anthracycline to reduce tumor growth. Levels of CITED2 were increased in gastric tumor samples from patients who had complete responses to epirubicin. CONCLUSIONS:
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Authors | Ivonne Regel, Lisa Merkl, Teresa Friedrich, Elke Burgermeister, Wolfgang Zimmermann, Henrik Einwächter, Ken Herrmann, Rupert Langer, Christoph Röcken, Ralf Hofheinz, Roland Schmid, Matthias P Ebert |
Journal | Gastroenterology
(Gastroenterology)
Vol. 143
Issue 1
Pg. 99-109.e10
(Jul 2012)
ISSN: 1528-0012 [Electronic] United States |
PMID | 22465428
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Anthracyclines
- Antibiotics, Antineoplastic
- CITED2 protein, human
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Indoles
- Repressor Proteins
- Trans-Activators
- Epirubicin
- Panobinostat
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Topics |
- Animals
- Anthracyclines
(pharmacology)
- Antibiotics, Antineoplastic
(pharmacology)
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Epirubicin
(pharmacology)
- Gene Expression
- Histone Deacetylase Inhibitors
(pharmacology)
- Humans
- Hydroxamic Acids
(pharmacology)
- Indoles
- Mice
- Mice, Transgenic
- Panobinostat
- Repressor Proteins
(genetics)
- Stomach Neoplasms
(drug therapy, genetics)
- Trans-Activators
(genetics)
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