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Optimization of photodynamic therapy response by survivin gene knockdown in human metastatic breast cancer T47D cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
30849 44508 2011 10 PDF Available
Title
Optimization of photodynamic therapy response by survivin gene knockdown in human metastatic breast cancer T47D cells
Abstract

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.

► After PDT-treatment, T47D breast cancer cells altered expression of survivin. ► The down-regulation of survivin sensitizes breast cancer cells to PDT-induced apoptosis. ► Survivin overexpression increased cell viability and reduced cell death in breast cancer cells treated with PDT. ► Survivin has a specific role in modulate PDT-mediated apoptotic and cytotoxicity response.

Keywords
Photodynamic therapy (PDT); Methyl ester ALA (MAL); Survivin; Apoptosis; Small interfering RNA (siRNA)
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Optimization of photodynamic therapy response by survivin gene knockdown in human metastatic breast cancer T47D cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 104, Issue 3, 2 September 2011, Pages 434–443
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us