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

Research output: Contribution to journalArticle

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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

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gemcitabine
HSP27 Heat-Shock Proteins
Pancreatic Neoplasms
Down-Regulation
KNK 437

All Science Journal Classification (ASJC) codes

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

Cite this

Taba, K., Kuramitsu, Y., Ryozawa, S., Yoshida, K., Tanaka, T., Mori-Iwamoto, S., ... 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

KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine. / Taba, Kumiko; Kuramitsu, Yasuhiro; Ryozawa, Shomei; Yoshida, Kanako; Tanaka, Toshiyuki; Mori-Iwamoto, Sayaka; Maehara, Shin Ichiro; Maehara, Yoshihiko; Sakaida, Isao; Nakamura, Kazuyuki.

In: Chemotherapy, Vol. 57, No. 1, 01.03.2011, p. 12-16.

Research output: Contribution to journalArticle

Taba, K, Kuramitsu, Y, Ryozawa, S, Yoshida, K, Tanaka, T, Mori-Iwamoto, S, Maehara, SI, 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, vol. 57, no. 1, pp. 12-16. https://doi.org/10.1159/000321019
Taba, Kumiko ; Kuramitsu, Yasuhiro ; Ryozawa, Shomei ; Yoshida, Kanako ; Tanaka, Toshiyuki ; Mori-Iwamoto, Sayaka ; Maehara, Shin Ichiro ; Maehara, Yoshihiko ; Sakaida, Isao ; Nakamura, Kazuyuki. / KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine. In: Chemotherapy. 2011 ; Vol. 57, No. 1. pp. 12-16.
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