Original Article

Cancer Gene Therapy (2004) 11, 309–316. doi:10.1038/sj.cgt.7700706 Published online 19 March 2004

Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells

Raquel T Lima1, Luís M Martins2, José E Guimarães1,3, Clara Sambade1,3 and M Helena Vasconcelos1,4

  1. 1IPATIMUP — Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
  2. 2Cancer Research UK, London, UK
  3. 3Faculty of Medicine of the University of Porto and Hospital S João, Porto, Portugal
  4. 4Department of Microbiology, Faculty of Pharmacy of the University of Porto, Porto, Portugal

Correspondence: Dr M Helena Vasconcelos, IPATIMUP, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal. E-mail: hvasconcelos@ipatimup.pt

Received 3 September 2003; Published online 19 March 2004.

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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.

Keywords:

siRNAs, RNAi, Bcl-2, xIAP

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