alexa KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine.
Gastroenterology

Gastroenterology

Journal of Gastrointestinal & Digestive System

Author(s): Taba K, Kuramitsu Y, Ryozawa S, Yoshida K, Tanaka T,

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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. Copyright © 2010 S. Karger AG, Basel. This article was published in Chemotherapy and referenced in Journal of Gastrointestinal & Digestive System

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