siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells.
Mol Cancer
; 8: 28, 2009 May 15.
Article
em En
| MEDLINE
| ID: mdl-19445670
ABSTRACT
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 micromol and 5.5 fold at 1 micromol 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
/
Condrossarcoma
/
Apoptose
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistencia a Medicamentos Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Mol Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2009
Tipo de documento:
Article