| Project/Area Number |
16591722
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Nara Medical University |
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Principal Investigator |
YANE Katsunari Nara Medical University, Medicine, Associate Professor, 医学部, 助教授 (40220199)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Takeo Nara Medical University, Medicine, Professor, 医学部, 教授 (60094554)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | head and neck cancer / molecular target / siRNA / radiotherapy / chemotherapy / p53 gene / chemical chaperone / NBS1 / 放射線増感 / DNA修復タンパク / 遺伝子導入 |
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| Research Abstract |
We have reported a new strategy using glycerol as a chemical chaperone for cancer therapy against mutant p53 (mp53) cancer cells. This strategy is based on conformational change in mp53 molecules restoring the normal function of mp53. Human tongue carcinoma (SAS) cells transfected with mutated p53 gene (SAS/mp53) showed CDDP-resistance compared with the cells with neo control gene (SAS/neo). When those cultured cells were pre-treated with glycerol, CDDP-induced apoptosis was enhanced by glycerol in SAS/mp53 cells but not in SAS/neo cells. In tumor-transplanted mice, the glycerol treatment to tumors enhanced growth delay induced by CDDP in mp53 tumors transplanted with SAS/mp53 cells, but not in wtp53 tumors transplanted with SAS/neo cells. Glycerol might be available for cancer chemotherapy in patients with mp53 tumors. Furthermore, we chose NBS1 as a molecular target to increase radiation sensitivity of cancer cell lines differing in p53 gene status (SAS/neo and SAS/mp53). NBS1 is essential for the repair of radiation induced DNA double-strand breaks (DSBs), Transfection of a DNA cassette expressing small interference RNA (siRNA) targeted for the NBS1 gene enhanced the radio sensitivity in SAS/neo and even more in SAS/mp53. These results suggest that siRNA targeted for NBS1 is a possible sensitizer for radiotherapy for the cancer patients.
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