title: Transfection of hypoxia-inducible factor-1 decoy oligodeoxynucleotides suppresses expression of vascular endothelial growth factor in oral squamous cell carcinoma cells.
abstract: Vasculature development is thought to be an important aspect in the growth and metastasis of solid tumors. Among the many angiogenic factors produced by tumor cells, vascular endothelial growth factor (VEGF) is considered to play a key role in angiogenic processes. VEGF synthesis is modulated by hypoxia-inducible factor-1 (HIF-1) function within the hypoxic microenvironment of growing cancer tissue. To inhibit HIF-1 activation, oligodeoxynucleotides (ODNs) were synthesized and transferred with either the consensus sequence for HIF-1 binding or a mutated form of this sequence. If we could transfer a large number of ODNs into the cancer cell nucleus, activated HIF-1 might bind to the ODNs, resulting in inhibition of hypoxia-induced VEGF synthesis. We transferred these ODNs into cultured oral squamous cell carcinoma cells (SAS cells) using the hemagglutinating virus of Japan (HVJ)-liposome method. Hypoxia-mediated expression of VEGF by cancer cells was suppressed by transfection of HIF-1 decoy ODNs, but not by mutated HIF-1 decoy ODNs. HIF-1 decoy ODN transfection also inhibited VEGF protein synthesis. These results suggest that transfection with HIF-1 decoy ODNs is effective for regulating tumor growth by reducing VEGF.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Imai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nariai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kanno
authors.forename: Joji
authors.initials: J
authors.lastname: Sekine
authors.forename: Mitsuho
authors.initials: M
authors.lastname: Onimaru
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mori
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics*; D008081:Liposomes; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D029082:Sendai virus / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A