期刊
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
卷 104, 期 3, 页码 434-443出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jphotobiol.2011.05.001
关键词
Photodynamic therapy (PDT); Methyl ester ALA (MAL); Survivin; Apoptosis; Small interfering RNA (siRNA)
资金
- Consejo Nacional de lnvestigaciones Cientificas y Tecnicas (CONICET)
- Agencia Nacional de Promocion Cientifica y Tecnologica (PICT)
- Secretaria de Ciencia y Tecnica (SECyT)
- Universidad Nacional de Rio Cuarto, Argentina
Photodynamic therapy (PDT) leads to the generation of cytotoxic oxygen species that appears to stimulate several different signaling pathways, some of which lead to cell death, whereas others mediate cell survival. In this context, we observed that PDT mediated by methyl-5-aminolevulinic acid as the photosensitizer resulted in over-expression of survivin, a member of the inhibitor of apoptosis (IAP) family that correlates inversely with patient prognosis. The role of survivin in resistance to anti-cancer therapies has become an area of intensive investigation. In this study, we demonstrate a specific role for survivin in modulating PDT-mediated apoptotic response. In our experimental system, we use a DNA vector-based siRNA, which targets exon-1 of the human survivin mRNA (pSil_1) to silence survivin expression. Metastatic T47D cells treated with both pSil_l and PDT exhibited increased apoptotic indexes and cytotoxicity when compared to single-agent treated cells. The treatment resulted in increased PARP and caspase-3 cleavage, a decrease in the Bcl-2/Bak ratio and no participation of heat shock proteins. In contrast, the overexpression of survivin by a survivin-expressed vector increased cell viability and reduced cell death in breast cancer cells treated with PDT. Therefore, our data suggest that combining PDT with a survivin inhibitor may attribute to a more favorable clinical outcome than the use of single-modality PDT. (C) 2011 Elsevier B.V. All rights reserved.
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