Protein-bound polysaccharide decreases invasiveness and proliferation in pancreatic cancer by inhibition of hedgehog signaling and HIF-1α pathways under hypoxia.

Hideya Onishi, Takafumi Morisaki, Fumihiko Nakao, Seiichi Odate, Takashi Morisaki, Mitsuo Katano

Index: Cancer Lett. 335(2) , 289-98, (2013)

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Abstract

To develop an effective therapeutic approach to pancreatic ductal adenocarcinoma (PDAC), we focused on the antitumor mechanism of protein-bound polysaccharide (PSK) under hypoxia. PSK decreased proliferation in PDAC cells under hypoxia but not normoxia. PSK also showed anti-tumor effects in vivo, inhibited invasiveness of PDAC cells, and decreased the expression of HIF-1α and hedgehog (Hh) signaling-related molecules under hypoxia. Inhibition of HIF-1α and Hh signaling reduced proliferation and invasiveness in PDAC cells under hypoxia. In conclusion, we found new PSK-related pathways in invasiveness and proliferation in PDAC under hypoxia. PSK may be a promising therapeutic drug to treat refractory PDAC.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.