Abstract
Antiapoptotic genes such as bcl-2 or xIAP may be responsible for resistance to apoptosis induced by cytotoxic drugs. The aim of this study was to investigate if downregulation of bcl-2 or xIAP by RNA interference (RNAi) would sensitize MCF-7 cells to etoposide and doxorubicin. FITC-siRNAs uptake was verified by fluorescence microscopy and downregulation of Bcl-2 or XIAP was confirmed by Western Blotting. Both siRNAs reduced the number of viable cells and increased cellular apoptosis. Treatment with siRNAs followed by treatment with etoposide or doxorubicin further reduced the number of viable cells, when compared to either of the treatments alone. Therefore, downregulation of bcl-2 or xIAP by RNAi enhances the effects of etoposide and doxorubicin.
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Acknowledgements
We thank Catarina A Silva (MD) for technical support in the initial experiments. This work was supported by FCT (Portugal), project POCTI/FCB/42754/2001 — Programa Operacional “Ciência, Tecnologia, Inovação” do Quadro Comunitário de Apoio (QCA) III, including FEDER funding. Raquel T Lima is a recipient of a young researcher grant from the referred project.
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Lima, R., Martins, L., Guimarães, J. et al. Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells. Cancer Gene Ther 11, 309–316 (2004). https://doi.org/10.1038/sj.cgt.7700706
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DOI: https://doi.org/10.1038/sj.cgt.7700706
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