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

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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 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. © 2009 Kim et al; licensee BioMed Central Ltd.

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Kim, D. W., Kim, K. O., Shin, M. J., Ha, J. H., Seo, S. W., Yang, J., & Lee, F. Y. (2009). siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells. Molecular Cancer, 8. https://doi.org/10.1186/1476-4598-8-28

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