| The histone deacetylase inhibitor vorinostat selectively sensitizes fibrosarcoma cells to chemotherapy. | |
| | |
MedLine Citation:
|
PMID: 20957741 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Soft tissue sarcoma (STS) is a rare malignancy that is generally resistant to chemotherapy. We investigated the ability of the histone deacetylase inhibitor vorinostat to sensitize STS cells versus normal fibroblasts to chemotherapy. Fibrosarcoma, leiomyosarcoma, and liposarcoma cells and normal fibroblasts were treated with vorinostat to determine effects on proliferation and basal apoptosis as measured by total cell number and cleaved caspase 3 staining. Effects on histone deacetylases (HDAC) activity were confirmed by Western blotting for acetylated histone H3. A clinically relevant dose of vorinostat that had no effect on basal apoptosis was selected to examine altered sensitivity to doxorubicin. The effects of vorinostat, doxorubicin, or the combination on fibrosarcoma growth in vivo were determined in a xenograft model. Tumor volume was measured biweekly and HDAC activity and cell death were assessed by immunohistochemical analysis of acetylated histone H3, cleaved caspase 3, and TUNEL staining. Vorinostat inhibited proliferation and induced histone acetylation without affecting basal apoptosis levels. Combined treatment with vorinostat and doxorubicin synergistically induced apoptosis in vitro in fibrosarcoma but not leiomyosarcoma, liposarcoma, or normal fibroblasts. In nude mice, the combination of vorinostat and doxorubicin inhibited fibrosarcoma xenograft growth further than either agent alone. Cell death, as measured by cleaved caspase 3 and TUNEL staining, was greatest in xenografts from mice treated with vorinostat and doxorubicin. Vorinostat inhibits growth and induces chemosensitivity in fibrosarcoma cells in vitro and in vivo, suggesting that the combination of vorinostat and chemotherapy may represent a novel treatment option for this STS subtype. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:623-632, 2011. |
| | |
Authors:
|
Erik R Sampson; Vinit Amin; Edward M Schwarz; Regis J O'Keefe; Randy N Rosier |
Publication Detail:
|
Type: Journal Article Date: 2010-10-18 |
Journal Detail:
|
Title: Journal of orthopaedic research : official publication of the Orthopaedic Research Society Volume: 29 ISSN: 1554-527X ISO Abbreviation: J. Orthop. Res. Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-02-21 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8404726 Medline TA: J Orthop Res Country: United States |
Other Details:
|
Languages: eng Pagination: 623-32 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Orthopaedic Research Society. |
Affiliation:
|
Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642. erik_sampson@urmc.rochester.edu. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: From hair to cornea: toward the therapeutic use of hair follicle-derived stem cells in the treatment...
Next Document: Effects of preexisting microdamage, collagen cross-links, degree of mineralization, age, and archite...