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Vol. 57, No. 1, 2011
Issue release date: March 2011
Section title: Experimental Chemotherapy
Chemotherapy 2011;57:12–16
(DOI:10.1159/000321019)

KNK437 Downregulates Heat Shock Protein 27 of Pancreatic Cancer Cells and Enhances the Cytotoxic Effect of Gemcitabine

Taba K.a, b · Kuramitsu Y.a · Ryozawa S.b · Yoshida K.a, b · Tanaka T.a · Mori-Iwamoto S.b · Maehara S.c · Maehara Y.c · Sakaida I.b · Nakamura K.a
Departments of aBiochemistry and Functional Proteomics and bGastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, and cDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Article / Publication Details

First-Page Preview
Abstract of Experimental Chemotherapy

Received: 4/8/2010
Accepted: 1/7/2010
Published online: 12/3/2010
Issue release date: March 2011

Number of Print Pages: 5
Number of Figures: 4
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE

Abstract

Background: Our previous proteomic study demonstrated that expression of heat shock protein 27 (HSP27) is upregulated in gemcitabine (GEM)-resistant pancreatic cancer cells and that it suppressed the cytotoxic effect of GEM on the cells. This report describes the benefits of a treatment strategy combining the HSP inhibitor KNK437 with GEM for GEM-resistant pancreatic cancer cells. Methods: We used 2 human pancreatic cancer cell lines, GEM-sensitive KLM1 and GEM-resistant KLM1-R. KLM1-R was treated with KNK437, and we examined the expression of HSP27 by Western blotting. The cytotoxicity of GEM and KNK437 for KLM1-R was investigated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Results: The expression of HSP27 in KLM1-R was dramatically reduced by KNK437. In addition, the in vitro antitumor cytotoxic effect of GEM on KLM1-R was enhanced by combination treatment with KNK437 compared to GEM alone. Conclusion: This study supports the potential therapeutic benefits of a treatment strategy combining KNK437 with GEM.

© 2010 S. Karger AG, Basel


  

Author Contacts

Yasuhiro Kuramitsu, MD, PhD
Department of Biochemistry and Functional Proteomics
Yamaguchi University Graduate School of Medicine
1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 (Japan)
Tel. +81 836 22 2213, Fax +81 836 22 2212, E-Mail climates@yamaguchi-u.ac.jp

  

Article Information

Received: April 8, 2010
Accepted after revision: July 1, 2010
Published online: December 3, 2010
Number of Print Pages : 5
Number of Figures : 4, Number of Tables : 0, Number of References : 26

  

Publication Details

Chemotherapy (International Journal of Experimental and Clinical Chemotherapy)

Vol. 57, No. 1, Year 2011 (Cover Date: March 2011)

Journal Editor: Sörgel F. (Nürnberg-Heroldsberg)
ISSN: 0009-3157 (Print), eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE


Article / Publication Details

First-Page Preview
Abstract of Experimental Chemotherapy

Received: 4/8/2010
Accepted: 1/7/2010
Published online: 12/3/2010
Issue release date: March 2011

Number of Print Pages: 5
Number of Figures: 4
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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