| IFN-γ combined with targeting of XIAP leads to increased apoptosis-sensitisation of TRAIL resistant pancreatic carcinoma cells. | |
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MedLine Citation:
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PMID: 22104728 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a specific and potent inducer of apoptosis in cancer cells, but the resistance of many tumour cells to TRAIL still represents a major hurdle for the clinical treatment of tumours with TRAIL. As apoptosis is regulated by the balance of activities of several anti-apoptotic factors and pro-apoptotic factors, we analysed the relative contribution of the two sides and found that down-regulation of Bcl-x(L) and in particular XIAP, but not c-Flip, sensitised the TRAIL resistant pancreatic cancer cell line Panc-1. A combination of both XIAP and Bcl-x(L) knock-downs showed no substantial added benefit indicating that both act in the same pathway. Notably, the degree of sensitisation by silencing of anti-apoptotic genes was further elevated by concomitantly increasing the pro-apoptotic potential in Panc-1 cells through over-expression of TRAIL-R1 or IFN-γ-mediated increases in caspase-8 levels. Similar sensitisation effects were obtained for another TRAIL-resistant pancreatic tumour cell line, AsPC-1. Our findings demonstrate that modulation of the balance between anti- and pro-apoptotic pathways from both sides by inhibition of apoptosis-antagonists and stimulation of pro-apoptotic factors provides the best way to enhance the anti-tumourigenic effect of TRAIL. |
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Authors:
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Chirlei Klein Büneker; Rui Yu; Laura Deedigan; Andrea Mohr; Ralf Michael Zwacka |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-2 |
Journal Detail:
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Title: Cancer letters Volume: - ISSN: 1872-7980 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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National University of Ireland, Galway, National Centre for Biomedical Engineering Science (NCBES), Galway, Ireland, Molecular Therapeutics Group, University Road, Galway, Ireland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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