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siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells

BACKGROUND: High expression of P-glycoprotein is one of the well-known mechanisms of chemoresistance in chondrosarcomas. However, the role of antiapoptotic proteins, a common mechanism responsible for chemoresistance in other tumors, has not been well studied in chondrosarcomas. We examined the impo...

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Autores principales: Kim, Dae Won, Kim, Kyung-Ok, Shin, Mike J, Ha, Jung Hee, Seo, Sung Wook, Yang, Jay, Lee, Francis Y
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689171/
https://www.ncbi.nlm.nih.gov/pubmed/19445670
http://dx.doi.org/10.1186/1476-4598-8-28
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author Kim, Dae Won
Kim, Kyung-Ok
Shin, Mike J
Ha, Jung Hee
Seo, Sung Wook
Yang, Jay
Lee, Francis Y
author_facet Kim, Dae Won
Kim, Kyung-Ok
Shin, Mike J
Ha, Jung Hee
Seo, Sung Wook
Yang, Jay
Lee, Francis Y
author_sort Kim, Dae Won
collection PubMed
description BACKGROUND: High expression of P-glycoprotein is one of the well-known mechanisms of chemoresistance in chondrosarcomas. However, the role of antiapoptotic proteins, a common mechanism responsible for chemoresistance in other tumors, has not been well studied in chondrosarcomas. We examined the importance of P-glycoprotein and antiapoptotic proteins in the chemoresistance to doxorubicin of two Grade II chondrosarcoma cell lines, JJ012 and SW1353. RESULTS: We confirmed that both chondrosarcoma cell types expressed P-glycoprotein and antiapoptotic proteins (Bcl-2, Bcl-xL and XIAP). siRNA knockdown as well as pharmacologic inhibitors of cell survival proteins (Bcl-2, Bcl-xL and XIAP) enhanced apoptosis of chemoresistant chondrosarcoma cells by up to 5.5 fold at 0.1 μmol and 5.5 fold at 1 μmol doxorubicin. These chemosensitizing effects were comparable to those of P-glycoprotein inhibition by siRNA or pharmacologic inhibitor. CONCLUSION: These findings suggest that antiapoptotic proteins play a significant role in the chemoresistance of chondrosarcoma cells independent of P-glycoprotein. Based on the results, a new siRNA-based therapeutic strategy targeting antiapoptotic genes can be designed to overcome the chemoresistance of chondrosarcomas which is often conferred by P-glycoprotein.
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spelling pubmed-26891712009-06-02 siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells Kim, Dae Won Kim, Kyung-Ok Shin, Mike J Ha, Jung Hee Seo, Sung Wook Yang, Jay Lee, Francis Y Mol Cancer Research BACKGROUND: High expression of P-glycoprotein is one of the well-known mechanisms of chemoresistance in chondrosarcomas. However, the role of antiapoptotic proteins, a common mechanism responsible for chemoresistance in other tumors, has not been well studied in chondrosarcomas. We examined the importance of P-glycoprotein and antiapoptotic proteins in the chemoresistance to doxorubicin of two Grade II chondrosarcoma cell lines, JJ012 and SW1353. RESULTS: We confirmed that both chondrosarcoma cell types expressed P-glycoprotein and antiapoptotic proteins (Bcl-2, Bcl-xL and XIAP). siRNA knockdown as well as pharmacologic inhibitors of cell survival proteins (Bcl-2, Bcl-xL and XIAP) enhanced apoptosis of chemoresistant chondrosarcoma cells by up to 5.5 fold at 0.1 μmol and 5.5 fold at 1 μmol doxorubicin. These chemosensitizing effects were comparable to those of P-glycoprotein inhibition by siRNA or pharmacologic inhibitor. CONCLUSION: These findings suggest that antiapoptotic proteins play a significant role in the chemoresistance of chondrosarcoma cells independent of P-glycoprotein. Based on the results, a new siRNA-based therapeutic strategy targeting antiapoptotic genes can be designed to overcome the chemoresistance of chondrosarcomas which is often conferred by P-glycoprotein. BioMed Central 2009-05-15 /pmc/articles/PMC2689171/ /pubmed/19445670 http://dx.doi.org/10.1186/1476-4598-8-28 Text en Copyright © 2009 Kim et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Kim, Dae Won
Kim, Kyung-Ok
Shin, Mike J
Ha, Jung Hee
Seo, Sung Wook
Yang, Jay
Lee, Francis Y
siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells
title siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells
title_full siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells
title_fullStr siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells
title_full_unstemmed siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells
title_short siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells
title_sort sirna-based targeting of antiapoptotic genes can reverse chemoresistance in p-glycoprotein expressing chondrosarcoma cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689171/
https://www.ncbi.nlm.nih.gov/pubmed/19445670
http://dx.doi.org/10.1186/1476-4598-8-28
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