Optimization of photodynamic therapy response by survivin gene knockdown in human metastatic breast cancer T47D cells.
J Photochem Photobiol B
; 104(3): 434-43, 2011 Sep 02.
Article
em En
| MEDLINE
| ID: mdl-21641815
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_1 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
/
Neoplasias da Mama
/
Proteínas Inibidoras de Apoptose
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Photochem Photobiol B
Assunto da revista:
BIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
Suíça