Document Detail


Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway.
MedLine Citation:
PMID:  20812347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Chondrosarcoma represents the second most common primary malignant bone tumor causing significant morbidity due to local recurrence and limited treatment options. Conventional cytotoxic chemotherapy has been proven to be largely ineffective to this sarcoma. Here we report that sorafenib is effective in growth inhibition of chondrosarcoma cell lines in vitro.
METHODS: Chondrosarcoma cell lines (SW1353 and CRL7891) were treated with sorafenib. Flow cytometry, DAPI assay, and Western blotting were employed to determine the effects of sorafenib in inhibitory proliferation and induce apoptosis in chondrosarcoma cells in vitro.
RESULTS: The results showed that sorafenib effectively inhibited cell growth and induced apoptosis in chondrosarcoma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Further more the expression levels of cyclin D1, Rb and anti-apoptotic proteins Bcl-xl and Mcl-1 significantly reduced, but no changes in Bcl-2 and Bax. We although detected the expression of Akt, JNK, p38 and their respective phosphoprotein, but did not found meaningful changes.
CONCLUSIONS: Our findings demonstrate that sorafenib inhibited the Ras/Raf/MAPK pathway in a time- and dose-dependent fashion in chondrosarcoma cell lines SW1353 and CRL7891 and suggest that sorafenib may be a new therapeutic option for patients with chondrosarcoma.
Authors:
Xinchang Lu; Xiaodong Tang; Wei Guo; Tingting Ren; Hui Zhao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of surgical oncology     Volume:  102     ISSN:  1096-9098     ISO Abbreviation:  J Surg Oncol     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0222643     Medline TA:  J Surg Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  821-6     Citation Subset:  IM    
Copyright Information:
2010 Wiley-Liss, Inc.
Affiliation:
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / metabolism
Benzenesulfonates / pharmacology*
Blotting, Western
Bone Neoplasms / drug therapy,  metabolism,  pathology
Cell Line, Tumor
Cell Proliferation / drug effects*
Chondrosarcoma / drug therapy*,  metabolism,  pathology
Cyclin D1 / metabolism
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*,  metabolism
Humans
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*,  metabolism
Phosphorylation / drug effects
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Pyridines / pharmacology*
Signal Transduction / drug effects
raf Kinases / antagonists & inhibitors*,  metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Benzenesulfonates; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/Pyridines; 0/sorafenib; 136601-57-5/Cyclin D1; EC 2.7.11.1/raf Kinases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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