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

doi:10.1016/j.canlet.2013.02.041

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

Cancer Lett. 2013 Jul 28;335(2):289-98. doi: 10.1016/j.canlet.2013.02.041. Epub 2013 Feb 26.

Authors

Hideya Onishi¹, Takafumi Morisaki, Fumihiko Nakao, Seiichi Odate, Takashi Morisaki, Mitsuo Katano

Affiliation

¹ Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ohnishi@surg1.med.kyushu-u.ac.jp

PMID: 23485726
DOI: 10.1016/j.canlet.2013.02.041

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibiotics, Antineoplastic / pharmacology
Carcinoma, Pancreatic Ductal / drug therapy*
Cell Cycle
Cell Hypoxia
Cell Line, Tumor
Cell Proliferation / drug effects
Female
Hedgehog Proteins / metabolism*
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Matrix Metalloproteinase 2 / biosynthesis
Matrix Metalloproteinase 9 / biosynthesis
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Transplantation
Pancreatic Neoplasms / drug therapy*
Polysaccharides
Proteoglycans / pharmacology*
RNA Interference
RNA, Small Interfering
Signal Transduction
Transcription Factors / genetics
Xenograft Model Antitumor Assays
Zinc Finger Protein GLI1

Substances

Antibiotics, Antineoplastic
GLI1 protein, human
HIF1A protein, human
Hedgehog Proteins
Hypoxia-Inducible Factor 1, alpha Subunit
Polysaccharides
Proteoglycans
RNA, Small Interfering
Transcription Factors
Zinc Finger Protein GLI1
polysaccharide-K
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9