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Cancer Chemotherapy and Pharmacology

Published in:

01-07-2009 | Original Article

Stable XIAP knockdown clones of HCT116 colon cancer cells are more sensitive to TRAIL, taxanes and irradiation in vitro

Authors: Kate Connolly, Richard Mitter, Morwenna Muir, Duncan Jodrell, Sylvie Guichard

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2009

Abstract

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.

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Title: Stable XIAP knockdown clones of HCT116 colon cancer cells are more sensitive to TRAIL, taxanes and irradiation in vitro
Authors: Kate Connolly
Richard Mitter
Morwenna Muir
Duncan Jodrell
Sylvie Guichard
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2009
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-008-0872-x

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Abstract

Purpose

Methods

Results

Conclusions

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