2000 Fiscal Year Final Research Report Summary
An attempt to develop new cancer therapy using decoy strategy
| Project/Area Number |
11557140
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
SHIRASUNA Kanemitsu KYUSHU UNIVERSITY Graduate School of Dental Science, Department of oral and Maxillofacial Surgery, Professor, 歯学研究院, 教授 (30093420)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Oral cancer / Invasion and metastasis / Protease / Transcription factors / Suppression of invasion / Gene therapy / Angiogenesis |
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| Research Abstract |
The ability of oral squamous cell carcinoma (SCC) cells to invade the surrounding tissue is a critical factor that affects the prognosis of patients. Invasive SCC cells degrade extracellular matrix (ECM) via an extracellular protease cascade, including urokinase-type plasminogen activator (uPA), plasmin, and the metalloprotease (MMP) family of collagenases. Vasculature development is also an important aspect in tumor invasion and metastasis. We previously showed that epidennal growth factor (EGF) and tumor necrosis factor α (TNF α) stimulate SCC invasion and productions of uPA and MMP-9 as well as vascular endothelial growth factor (VEGF) which is one of most potent angigenic factors. These stimulations by EGF and TNF α were strongly inhibited by dexamethasone. The results also showed that antagonistic effects of dexamethasone and EGF or TNF α are mediated through transcription factors, Sp1, AP1 and NF- κ B, suggesting that these transcription factors will be target for cancer therapy. In this study, we synthesized several oligodeoxynucleotides (ODNs) with the consensus sequence for Sp1, AP1 or NF- κ B binding (Sp1, AP1 or NF- κ B docoy ODNs) and a mutated form of each each sequence. Using the Hemagglutinating virus of Japan (HVJ)-liposome method, we transfected ODNs into SCC cells. TNF α -stimulated expression of VEFG, TGF β, tissue factor, and uPA and invasiveness in SCC cells could be inhibited by transfection of Sp1 decoy ODNs. AP1 and NF- κ B decoy ODNs inhibited EGF- and TNF α -induced uPA, uPA receptor and MMP-9 expression in SCC cells. However, inhibitory effects of these decoy ODNs on cell invasion were very low as compared to those by dexamethasone. Further studies will be required to establish whether Sp1, AP1 and NF- κ B docoy strategies are effective for tumor control by reducing invasiveness.
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Research Products
(2 results)
