| Project/Area Number |
13470181
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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 |
Radiation science
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| Research Institution | Faculty of Medical Sciences, University of Fukui |
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Principal Investigator |
MATSUMOTO Hideki Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Associate Professor, 医学部, 助教授 (40142377)
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| Co-Investigator(Kenkyū-buntansha) |
JIN Zhao-hui Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Assistant Professor, 医学部, 助手 (70324150)
HAYASHI Sachiko Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Assistant Professor, 医学部, 助手 (00218570)
KANO Eiichi Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Professor, 医学部, 教授 (70065910)
HATASHITA Masanori The Wakasa Wan Energy Research Center, Research and Development, Researcher, 物性バイオグループ, 主査 (40359237)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | SCC / NSCLC / Radiotherapy / Hyperthermia / Drug for angina pectoris / p53 / Hsp70 / Apoptosis / apoptopsis / 放射線治療 / 温熱療法 / NOラジカル発生剤 / バイスタンダー効果 / Hsp72 / 放射線 / Nitric oxide / Nitric oxide発生剤 / 放射線感受性 / 細胞間シグナル伝達系 / アポトーシス |
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| Research Abstract |
We examined effects of a nitric oxide-generating agent, isosorbide dinitrate(ISDN), which is a quite popular drug for angina pectoris, on radiotherapy and hyperthermia to cancer cells in vifro and in vivo from an aspect of p53 functions.Transplantable p53-deficient human non-small cell lung cancer(NSCLC) H1299 cells were transfected with a vector carrying wild-type, mutant p53 gene or a neomycin-resistant gene(neo)alone as a control.
Radiosensitivity and thermosensitivity at 44℃ of these transfectants in vitro was increased with ISDN (0.3 mM) in a p53-independent manner, although ISDN revealed no cytotoxicity at 37℃ in vitro. Western blot analysis indicated that the increase of thermosensitivity was partially due to a stimulation of decay of heat-induced Hsp72.Growth delay of these transplanted tumors after irradiation at 10 Gy or heating at 43℃ in vivo was enhanced with ISDN (0.3 mM) regardless of their p53 gene status, although lSDN revealed no effect on tumor growth.Immunohistochemical analysis(TUNEL method) indicated that the enhancement of tumor growth delay was partially due to induction of p53-independent apoptosisin both cases.
These findings suggested that a p53-independent apoptosis induced an efficient cell killing and tumor growth delay by combined treatment with radiation or hyperthermia and ISDN.
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