Document Detail

RAIDD expression is impaired in multidrug resistant osteosarcoma cell lines.
MedLine Citation:
PMID:  19125251     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To identify the apoptosis genes involved in the multidrug resistant phenotype of osteosarcoma. METHODS: Multidrug resistant human osteosarcoma cell line (U-2 OS MR) and a drug sensitive parental cell line (U-2 OS) were both treated with paclitaxel and analyzed by the gene array containing 96 apoptosis associated genes. The different expression of the special apoptosis associated genes were further analyzed by Western blot in the multidrug resistant osteosarcoma cell lines (U-2 OS MR, KH OS R2) and the drug sensitive parental cell lines (U-2 OS, KH OS). One of the disregulated gene, RAIDD, was transfected into the multidrug resistant osteosarcoma cells for functional studies. RESULTS: RAIDD showed signs of significant expression in the U-2 OS cells after being treated with paclitaxel (P < 0.01). However, the induction of RAIDD did not occur in U-2 OS MR cells (P = 0.2). Subsequent analysis by Western blot confirmed the deficiency of the expression of RAIDD protein in U-2 OS MR. On the contrary, the expression of RAIDD could be significantly induced by paclitaxel and doxorubicin in U-2 OS cells as both time and dosage were deciding factors. It also demonstrated the cleavage of PARP associated with RAIDD expression in U-2 OS cells, but not however in U-2 OS MR cells after being treated with paclitaxel or doxorubicin. Similar results were found in osteosarcoma multidrug resistant cell line KH OS R2 and the drug sensitive parental cell line KH OS. Furthermore, over-expression of RAIDD in multidrug resistant cell lines could possibly reverse drug resistant phenotypes. CONCLUSION: This study indicate that impaired expression of RAIDD in drug induced apoptosis may play a role in the multidrug resistance of osteosarcoma cells.
Cao Yang; Francis J Hornicek; Kirkham B Wood; Joseph H Schwab; Henry Mankin; Zhenfeng Duan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-01-06
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  64     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-08     Completed Date:  2009-06-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  607-14     Citation Subset:  IM    
Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
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MeSH Terms
Antibiotics, Antineoplastic / pharmacology
Antineoplastic Agents, Phytogenic / administration & dosage,  pharmacology
Apoptosis / genetics*
Blotting, Western
CRADD Signaling Adaptor Protein / genetics*
Cell Line, Tumor
Dose-Response Relationship, Drug
Doxorubicin / pharmacology
Drug Resistance, Multiple
Drug Resistance, Neoplasm*
Gene Expression Regulation, Neoplastic*
Oligonucleotide Array Sequence Analysis / methods
Osteosarcoma / genetics*
Paclitaxel / administration & dosage,  pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Time Factors
Grant Support
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antineoplastic Agents, Phytogenic; 0/CRADD Signaling Adaptor Protein; 0/CRADD protein, human; 23214-92-8/Doxorubicin; 33069-62-4/Paclitaxel; EC Polymerases

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