Document Detail


Stable XIAP knockdown clones of HCT116 colon cancer cells are more sensitive to TRAIL, taxanes and irradiation in vitro.
MedLine Citation:
PMID:  19034449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To develop a model of X-linked inhibitor of apoptosis (XIAP) down regulation in colorectal cancer cell lines. This may be used to determine whether combination strategies have clinical potential. METHODS: A series of clones were developed using short hairpin RNA (shRNA) against XIAP stably expressed in HCT116 cells. XIAP mRNA and protein levels were established by RT-PCR and Immunoblot, respectively. GeneChip microarrays confirmed XIAP knockdown and absence of compensation by other IAP members. RESULTS: Four XIAP knockdown cell lines show 82-93% reduction in XIAP mRNA and 67-89% reduction in protein when compared to four luciferase control cell lines. XIAP knockdown sensitises cells to rhTRAIL by a factor of 3, to paclitaxel and docetaxel by a factor of >2 and, to a lesser extent, radiotherapy (20% enhancement). CONCLUSIONS: Clinical trials with XIAP antisense continue, and these data suggest combination studies with agents such as rhTRAIL and taxanes should be undertaken.
Authors:
Kate Connolly; Richard Mitter; Morwenna Muir; Duncan Jodrell; Sylvie Guichard
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-26
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  64     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-01     Completed Date:  2009-06-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  307-16     Citation Subset:  IM    
Affiliation:
University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh, EH4 2XR, UK. kateconnolly@doctors.org.uk
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MeSH Terms
Descriptor/Qualifier:
Animals
Caspases / metabolism
Cell Proliferation / drug effects,  radiation effects
Colonic Neoplasms / drug therapy*,  genetics,  radiotherapy*
Flow Cytometry
Gamma Rays
Gene Expression Profiling
Gene Knockdown Techniques
Humans
Immunoblotting
Mice
Mice, Nude
Oligonucleotide Array Sequence Analysis
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
TNF-Related Apoptosis-Inducing Ligand / pharmacology*
Taxoids / pharmacology*
Tumor Cells, Cultured
X-Linked Inhibitor of Apoptosis Protein / genetics*
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
C96/A4743//Cancer Research UK
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/RNA, Small Interfering; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Taxoids; 0/X-Linked Inhibitor of Apoptosis Protein; 0/XIAP protein, human; EC 3.4.22.-/Caspases

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