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Biochem Biophys Res Commun. 2007 Jan 5;352(1):220-5. Epub 2006 Nov 10.

Aurora kinase inhibition downregulates NF-kappaB and sensitises tumour cells to chemotherapeutic agents.

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1
Centre for Cancer Therapeutics, The Institute of Cancer Research, Cancer Research UK, Belmont, Surrey SM2 5NG, UK.

Abstract

We have identified that Aurora-A activates NF-kappaB via IkappaBalpha phosphorylation. Here, we analysed different human tumour cell types for their NF-kappaB activity. We found that there is an association between cell resistance to chemotherapeutic agents and NF-kappaB activation. A549 human lung adenocarcinoma cells and SKOV3 human ovarian cancer cells have high levels of NF-kappaB and are resistant to cytotoxic agents such as adriamycin and VP-16 (etoposide). We also found that in A549 and SKOV3 cells treated with a small molecule inhibitor towards Aurora kinases, the NF-kappaB activity was downregulated and the efficacy of cytotoxic drugs was enhanced. In addition, the transcriptional targets Bcl-XL and Bcl-2 were downregulated. This study provides evidence for a potential mechanism of chemoresistance and may be useful for the enhancement of certain chemotherapeutics regimens.

PMID:
17113039
DOI:
10.1016/j.bbrc.2006.11.004
[Indexed for MEDLINE]
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