| Project/Area Number |
17390540
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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 | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Kyushu University |
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Principal Investigator |
TAKENOSHITA Yasuharu Kyushu University, School of Dental Science, Ass. Prof (50117157)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIBASHI Hiroaki Shimane Univ, Faculty of Medicine, Ass. Prof (90254630)
NAKAGAWA Kazunori Kyushu Univ., School of Medical Science, Ass. Prof (50217668)
石橋 浩晃 九州大学, 大学院歯学研究院, 助手 (90257668)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2005: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | Oral Cancer / Multi-drug Resistance / Gene Therapy |
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| Research 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. The synthesis of VEGF is modulated through hypoxia-inducible factor-1 (HIF-1) function following hypoxic microenvironment of growing cancer tissue. HIF-1 transactivation by hypoxia also plays an important role in chemosensitivity for anticancer agents via induction of multidrug resistance (MDR1).To inhibition of 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 ODNs excessively in the cancer cell nucleus, activated HIF-1 might bind to the ODNs, resulting in inhibition of hypoxia-induced VEGF and MDR1 synthesis. We transferred these ODNs into cultured oral squamous cell carcinoma cells (SAS cells) and adenoid cystic carcinoma cells (ACCS cells) using the hemagglutinating virus of Japan (HVJ)-liposome method. The hypoxia-mediated expression of VEGF and MDR1 by the cancer cells could be simultaneously suppressed by transfection of HIF-1 decoy ODNs, but not by mutated HIF-1 decoy ODNs. HIF-1 decoy ODNs transfection also inhibited the protein synthesis of VEGF and P-glycoprotein, and increased the drug sensitivity for anti-cancer agents. These results suggest that the transfection with HIF-1 decoy ODNs would be simultaneously effective for regulating tumor growth and chemosensitivity by reducing VEGF and MDR1.
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