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

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

Chemotherapy. 2011;57(1):12-6.

PMID: 21124027

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP218924255	KNK437		218924-25-5	Price

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