Journal
CANCER LETTERS
Volume 335, Issue 2, Pages 289-298Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.02.041
Keywords
PSK; Hedgehog signaling; HIF-1 alpha; Pancreatic cancer; Hypoxia
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Funding
- JSPS KAKENHI [24390303]
- Grants-in-Aid for Scientific Research [23659616, 24390303] Funding Source: KAKEN
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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-1 alpha and hedgehog (Hh) signaling-related molecules under hypoxia. Inhibition of HIF-1 alpha 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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
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