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

Kumiko Taba, Yasuhiro Kuramitsu, Shomei Ryozawa, Kanako Yoshida, Toshiyuki Tanaka, Sayaka Mori-Iwamoto, Shin Ichiro Maehara, Yoshihiko Maehara, Isao Sakaida, Kazuyuki Nakamura

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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.

Original languageEnglish
Pages (from-to)12-16
Number of pages5
JournalCHEMOTHERAPY
Volume57
Issue number1
DOIs
Publication statusPublished - Mar 1 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)
  • Infectious Diseases

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    Taba, K., Kuramitsu, Y., Ryozawa, S., Yoshida, K., Tanaka, T., Mori-Iwamoto, S., Maehara, S. I., Maehara, Y., Sakaida, I., & Nakamura, K. (2011). KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine. CHEMOTHERAPY, 57(1), 12-16. https://doi.org/10.1159/000321019