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Cancer Chemother Pharmacol. 2009 Jul;64(2):307-16. doi: 10.1007/s00280-008-0872-x. Epub 2008 Nov 26.

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

Author information

1
University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh, EH4 2XR, UK. kateconnolly@doctors.org.uk

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.

PMID:
19034449
DOI:
10.1007/s00280-008-0872-x
[Indexed for MEDLINE]

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