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

研究成果: ジャーナルへの寄稿学術誌査読

5 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)3945-3952
ページ数8
ジャーナルAnticancer research
36
8
出版ステータス出版済み - 8月 2016

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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