Investigation of the participation in anticancer agent tolerance of microRNA in oral cancer

microRNA参与口腔癌抗癌药物耐受的研究

• 批准号: 23792369
• 负责人: YAMAKAWA Nobuhiro
• 金额: $ 2.75万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23792369/
• 关键词: 5-FU; BRCA2; UCN; microRNA

Using cells derived from DNA repair enzyme deficiency Chinese hamster lung fibroblast, we investigated the target candidate what raised cytotoxicity reaction of 5 -FU in the DNA repair course. We measured a survival rate and the measurement of the quantity of DNA double-strand break using BRCA2 deficient cells derived from Chinese hamster lung fibroblast and ku80 deficient cells and each parent root cell. As a result, the BRCA2 deficient cells accepted the cytotoxicity reaction that had high approximately 2.5 times by 5-FU. Furthermore, with the BRCA2deficient cells, the repair delay of the DNA double-strand break to result from 5-FU treatment as compared with the parent root cells was confirmed.As an additional experiment, we confirmed a sensibilization effect of 5-FU using the SAS cells which were cells and the tongue cancer cells of the Chinese Hamster Lung Fibroblast (BRCA2 wild-type) origin using UCN which was BRCA2 and the Chk1 inhibitor with the relation. A low bottom significantly accepted the survival rate of cells by using UCN together as compared with 5 -FU use alone in both cells. In other words we were able to achieve sensitivity of 5-FU by inhibiting homologous recombination restoration.

本研究以DNA修复酶缺陷的中国仓鼠肺成纤维细胞为研究对象，探讨了在DNA修复过程中提高5 -FU细胞毒性反应的靶点。使用来自中国仓鼠肺成纤维细胞的BRCA 2缺陷型细胞和ku 80缺陷型细胞以及各亲本根细胞，测定了存活率和DNA双链断裂量。结果，BRCA 2缺陷细胞接受了5-FU的约2.5倍的高细胞毒性反应。此外，对于BRCA 2缺陷细胞，与亲本根细胞相比，证实了由5-FU处理引起的DNA双链断裂的修复延迟。我们用中国人肺成纤维细胞的SAS细胞和舌癌细胞证实了5-FU的增敏作用（BRCA 2野生型）来源使用UCN，这是BRCA 2和Chk 1抑制剂的关系。在两种细胞中，与单独使用5 -FU相比，联合使用UCN的细胞存活率明显较低。换句话说，我们能够通过抑制同源重组恢复来实现5-FU的敏感性。

项目成果

Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

• DOI: 10.1016/j.bbrc.2012.06.004
• 发表时间: 2012-07-13
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Nakagawa, Yosuke;Takahashi, Akihisa;Ohnishi, Takeo
• 通讯作者: Ohnishi, Takeo

口腔がんにおける重粒子線照射による生存シグナルを介した細胞周期および細胞死の制御

口腔癌中重离子束照射通过生存信号控制细胞周期和细胞死亡

• 发表时间: 2012
• 作者: 仲川洋介;梶原淳久;山川延宏;桐田忠昭
• 通讯作者: 桐田忠昭

DNA 修復経路を標的とした 5-FU 増感効果の検討

针对 DNA 修复途径的 5-FU 致敏效果检查

• 发表时间: 2012
• 作者: Yousuke Nakagawa;Akihisa Takahashi;Athuhisa Kajihara;Nobuhiro Yamakawa;Yuichiro Imai;Ichiro Ota;Noritomo Okamoto;Eiichiro Mori;Taichi Noda;Yoshiya Furusawa;Tadaaki Kirita;Takeo Ohnishi;仲川洋介;仲川洋介
• 通讯作者: 仲川洋介