title: Protein-bound polysaccharide decreases invasiveness and proliferation in pancreatic cancer by inhibition of hedgehog signaling and HIF-1α pathways under hypoxia.
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.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ohnishi@surg1.med.kyushu-u.ac.jp
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakao
authors.forename: Seiichi
authors.initials: S
authors.lastname: Odate
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy*; D002453:Cell Cycle; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011134:Polysaccharides; D011509:Proteoglycans / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000071676:Zinc Finger Protein GLI1
chemical_list: D000903:Antibiotics, Antineoplastic; C400551:GLI1 protein, human; C497442:HIF1A protein, human; D053823:Hedgehog Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011134:Polysaccharides; D011509:Proteoglycans; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C010770:polysaccharide-K; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9