Protein-bound polysaccharide-k inhibits hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, suppressing the malignant phenotype in pancreatic cancer

Akio Yamasaki, Hideya Onishi, Akira Imaizumi, Makoto Kawamoto, Akiko Fujimura, Yasuhiro Oyama, Mitsuo Katano

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Abstract

Hedgehog signaling is activated in pancreatic cancer and could be a therapeutic target. We previously demonstrated that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) contribute to the hypoxia-induced up-regulation of Smoothened (SMO) transcription. We have also shown that protein-bound polysaccharide-K (PSK) could be effective for refractory pancreatic cancer that down-regulates SMO transcription under hypoxia. In this study, we evaluated whether the anticancer mechanism of PSK involves inhibiting RBPJ and MAML3 expression under hypoxia. PSK reduced SMO, MAML3 and RBPJ expression in pancreatic cancer cells under hypoxia. PSK also blocked RBPJ-induced invasiveness under hypoxia by inhibiting matrix metalloproteinase expression. Lastly, we showed that PSK attenuated RBPJ-induced proliferation both in vitro and in vivo. These results suggest that PSK suppresses Hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, inhibiting the induction of a malignant phenotype in pancreatic cancer. Our results may lead to development of new treatments for refractory pancreatic cancer using PSK as a Hedgehog inhibitor.

Original languageEnglish
Pages (from-to)3945-3952
Number of pages8
JournalAnticancer research
Volume36
Issue number8
Publication statusPublished - Aug 2016

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Pancreatic Neoplasms
Polysaccharides
Down-Regulation
Phenotype
Proteins
Cell Hypoxia
krestin
Hypoxia
Matrix Metalloproteinases
Genetic Recombination
Immunoglobulins
Carrier Proteins
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Protein-bound polysaccharide-k inhibits hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, suppressing the malignant phenotype in pancreatic cancer. / Yamasaki, Akio; Onishi, Hideya; Imaizumi, Akira; Kawamoto, Makoto; Fujimura, Akiko; Oyama, Yasuhiro; Katano, Mitsuo.

In: Anticancer research, Vol. 36, No. 8, 08.2016, p. 3945-3952.

Research output: Contribution to journalArticle

Yamasaki, Akio ; Onishi, Hideya ; Imaizumi, Akira ; Kawamoto, Makoto ; Fujimura, Akiko ; Oyama, Yasuhiro ; Katano, Mitsuo. / Protein-bound polysaccharide-k inhibits hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, suppressing the malignant phenotype in pancreatic cancer. In: Anticancer research. 2016 ; Vol. 36, No. 8. pp. 3945-3952.
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