DSpace university logo mark
Advanced Search
Japanese | English 

NAOSITE : Nagasaki University's Academic Output SITE > Graduate School of Biomedical Sciences > Articles in academic journal >

Imatinib enhances docetaxel-induced apoptosis through inhibition of nuclear factor-κB activation in anaplastic thyroid carcinoma cells


File Description SizeFormat
Thy22_717.pdf1.76 MBAdobe PDFView/Open

Title: Imatinib enhances docetaxel-induced apoptosis through inhibition of nuclear factor-κB activation in anaplastic thyroid carcinoma cells
Authors: Kim, EunSook / Matsuse, Michiko / Saenko, Vladimir / Suzuki, Keiji / Ohtsuru, Akira / Mitsutake, Norisato / Yamashita, Shunichi
Issue Date: 29-Jun-2012
Publisher: Mary Ann Liebert Inc.
Citation: Thyroid, 22(7), pp.717-724; 2012
Abstract: Background: We previously reported the partial effectiveness of imatinib (also known as STI571, Glivec, or Gleevec) on anaplastic thyroid cancer (ATC) cells. Imatinib is a selective tyrosine kinase inhibitor that has been used for various types of cancer treatments. Recently, several reports have demonstrated that imatinib enhanced the sensitivity of cancer cells to other anticancer drugs. In this study, therefore, we investigated whether imatinib enhances the antitumor activity of docetaxel in ATC cells. Methods: Two ATC cell lines, FRO and KTC-2, were treated with imatinib and/or docetaxel. Cell survival assay and flow cytometry for annexin V were used to assess the induction of apoptosis. Changes of pro- and antiapoptotic factors were determined by Western blot. Nuclear factor-κB (NF-κB) activity was measured by DNA-binding assay. Tumor growth was also investigated in vivo. Results: The combined treatment significantly enhanced apoptosis compared with single treatment. ATC cells themselves expressed high levels of antiapoptotic factors, X-linked inhibitor of apoptosis (XIAP), and survivin. The treatment with docetaxel alone further increased their expressions; however, the combined treatment blocked the inductions. Although imatinib alone had no effect on NF-κB background levels, combined treatment significantly suppressed the docetaxel-induced NF-κB activation. Further, the combined administration of the drugs also showed significantly greater inhibitory effect on tumor growth in mice xenograft model. Conclusions: Imatinib enhanced antitumor activity of docetaxel in ATC cells. Docetaxel seemed to induce both pro- and antiapoptotic signaling pathways in ATC cells, and imatinib blocked the antiapoptotic signal. Thus, docetaxel combined with imatinib emerges as an attractive strategy for the treatment of ATC.
Keywords: caspase 3 / docetaxel / I kappa B alpha / imatinib / immunoglobulin enhancer binding protein / lipocortin 5 / nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase / survivin / transcription factor RelA / X linked inhibitor of apoptosis / anaplastic thyroid cancer / animal experiment / animal model / antineoplastic activity / apoptosis / article / cancer inhibition / carcinoma cell / cell count / cell growth / cell survival / controlled study / DNA binding / flow cytometry / human / human cell / human tissue / in vivo study / male / mouse / nonhuman / priority journal / protein cleavage / protein expression / signal transduction / tumor growth / tumor volume / tumor xenograft / Western blotting
URI: http://hdl.handle.net/10069/29682
ISSN: 10507256
DOI: 10.1089/thy.2011.0380
Rights: This is a copy of an article published in the Thyroid © 2012 copyright Mary Ann Liebert, Inc.; Thyroid is available online at: http://online.liebertpub.com.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/29682

All items in NAOSITE are protected by copyright, with all rights reserved.

 

Valid XHTML 1.0! Copyright © 2006-2015 Nagasaki University Library - Feedback Powerd by DSpace