Optimization of Photodynamic Therapy Response by Survivin Gene Knockdown in Human Metastatic Breast Cancer T47d Cells

INGRID S. COGNO, ; NATALIA B. RUMIE VITTAR; MARIA JULIA LAMBERTI; VIVIANA A. RIVAROLA

JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY

ELSEVIER SCIENCE SA

Año: 2011

1011-1344

AbstractPhotodynamic therapy (PDT) leads to the generation of cytotoxic oxygen species that appears tostimulate several different signaling pathways, some of which lead to cell death, whereas othersmediate cell survival. In this context, we observed that PDT mediated by methyl-5-aminolevulinicacid as the photosensitizer resulted in over-expression of survivin, a member of the inhibitor ofapoptosis (IAP) family that correlates inversely with patient prognosis. The role of survivin inresistance to anti-cancer therapies has become an area of intensive investigation. In this study, wedemonstrate a specific role for survivin in modulating PDT-mediated apoptotic response. In ourexperimental system, we use a DNA vector-based siRNA, which targets exon-1 of the humansurvivin mRNA (pSil_1) to silence survivin expression. Metastatic T47D cells treated with bothpSil_1 and PDT exhibited increased apoptotic indexes and cytotoxicity when compared to singleagenttreated cells. The treatment resulted in increased PARP and caspase-3 cleavage, a decrease inthe Bcl-2/Bak ratio and no participation of heat shock proteins. In contrast, the overexpression ofsurvivin by a survivin-expressed vector increased cell viability and reduced cell death in breastcancer cells treated with PDT. Therefore, our data suggest that combining PDT with a survivininhibitor may attribute to a more favorable clinical outcome than the use of single-modality PDT.