| Project/Area Number |
24659902
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Surgical dentistry
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| Research Institution | Nara Medical University |
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Principal Investigator |
KIRITA TADAAKI 奈良県立医科大学, 医学部, 教授 (70201465)
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| Co-Investigator(Kenkyū-buntansha) |
KAJIHARA Atsuhisa 奈良県立医科大学, 医学部, 研究員 (00382317)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | DNA repair / 5-fluorouracil / BRCA2 / oral cancer / DNA修復 / 口腔がん / 化学療法 / 5-FU |
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| Research Abstract |
5-FU is widely used in clinical cancer therapy. 5-FU induces DNA double-strand breaks (DSBs). The aim of this study was to learn more about pathways which are involved in the repair of 5-FU-induced DSBs. Cell survival after drug treatment was examined with colony forming assays using Chinese hamster lung fibroblast cells, or Chinese hamster ovary cell lines which are deficient in DSB repair pathways involving the homologous recombination repair-related genes BRCA2 and XRCC2, and the non-homologous end joining repair-related genes DNA-PKcs and Ku80. It was found that BRCA2 was involved in such repair, and might be effectively targeted to inhibit the repair of 5-FU damage. Observations showed that a knockdown of BRCA2 using small interference RNA suppression increased sensitivity to 5-FU in human oral cancer SAS and HSC3 cells. These findings suggest that down regulation of BRCA2 might be useful for sensitizing tumor cells during 5-FU chemotherapy.
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