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

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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

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.

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).

Clinical trials with XIAP antisense continue, and these data suggest combination studies with agents such as rhTRAIL and taxanes should be undertaken.

Original languageEnglish
Pages (from-to)307-316
Number of pages10
JournalCancer chemotherapy and pharmacology
Volume64
Issue number2
DOIs
Publication statusPublished - Jul 2009

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