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Transfection of hypoxia‐inducible factor‐1 decoy oligodeoxynucleotides suppresses expression of vascular endothelial growth factor in oral squamous cell carcinoma cells
Author(s) -
Imai Mie,
Ishibashi Hiroaki,
Nariai Yoshiki,
Kanno Takahiro,
Sekine Joji,
Onimaru Mitsuho,
Mori Yoshihide
Publication year - 2012
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2012.01161.x
Subject(s) - decoy , transfection , vascular endothelial growth factor , cancer research , hypoxia inducible factors , cell culture , biology , cell growth , vascular endothelial growth factor a , cell , cancer cell , angiogenesis , growth factor , hif1a , microbiology and biotechnology , cancer , vegf receptors , biochemistry , receptor , gene , genetics
J Oral Pathol Med (2012) 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.