Establishment of cancer therapytargeted for DNA dependent protein kinase and investigation of its predictive factor

DNA依赖性蛋白激酶靶向癌症治疗的建立及其预测因素的研究

• 批准号: 22501031
• 负责人: ARAGANE Naoko
• 金额: $ 2.75万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22501031/
• 关键词: バイオマーカー; 肺癌; DNA依存性キナーゼ; トポイソメラーゼIIα; DNA二重鎖切断; 成人T細胞性白血病

NK314, a dual inhibitor of DNA dependent protein kinase (DNA-PK) and topoisomerase IIαpotently inhibited cell growth of adult T cell leukemia and lung cancer cell lines. The inhibitory effect was mediated through enhancement of DNA double strand breaks and prolonged inhibitory effect ofDNA repair. As for the predictive factors for DNA-PK inhibitors, protein level of hnRNP B1, an RNA binding protein, was strongly associated with that of DNA-PKcs. However, the inhibitory effect of cell growth of lung cancer cells was not statistically associated with protein levels of DNA-PKcs nor hnRNP B1. Further investigation for seeking the predictive factors would be needed.

NK314是DNA依赖性蛋白激酶（DNA- pk）和拓扑异构酶i α的双重抑制剂，能有效抑制成人T细胞白血病和肺癌细胞系的细胞生长。抑制作用是通过增强DNA双链断裂和延长DNA修复抑制作用介导的。对于DNA-PK抑制剂的预测因素，RNA结合蛋白hnRNP B1的蛋白水平与DNA-PKcs的蛋白水平密切相关。然而，肺癌细胞生长的抑制作用与DNA-PKcs和hnRNP B1蛋白水平无统计学相关性。需要进一步调查以寻找预测因素。

项目成果

DNA-dependent protein kinase as a molecular target of chemotherapy on hematological malignancy.

DNA依赖性蛋白激酶作为血液恶性肿瘤化疗的分子靶点。

• 发表时间: 2010
• 作者: 末岡 栄三朗

DNA dependent protein kinase as a new molecular target for treatment of non-small cell lung cancer

DNA依赖性蛋白激酶作为治疗非小细胞肺癌的新分子靶点

• 发表时间: 2012
• 作者: Naoko Aragane;Akemi Sato;Kentaro Iwanaga;Naomi Kobayash;Shinya Kimura;Eisaburo Sueoka.
• 通讯作者: Eisaburo Sueoka.

DNA-dependent protein kinase as a promising molecular target for the treatment of adult T-cell leukemia-lymphoma

DNA依赖性蛋白激酶作为治疗成人T细胞白血病-淋巴瘤的有前景的分子靶点

• 发表时间: 2011
• 作者: Hisatomi T;Sueoka-Aragane N;Sato A;Tomimasu R;Ide M;Kunimasa A;Okamoto K;Kimura S;Sueoka E
• 通讯作者: Sueoka E

NK314 potentiates antitumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase IIα and DNA-dependent protein kinase

• DOI: 10.1182/blood-2010-02-270439
• 发表时间: 2011-03-31
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Hisatomi, Takashi;Sueoka-Aragane, Naoko;Sueoka, Eisaburo
• 通讯作者: Sueoka, Eisaburo

Dual targeting therapy on topoisomerase IIα and DNA-dependent protein kinase is a promising strategy for adult T-cell leukemia-lymphom

拓扑异构酶 IIα 和 DNA 依赖性蛋白激酶双靶向治疗是治疗成人 T 细胞白血病-淋巴瘤的一种有前途的策略

• 发表时间: 2012
• 作者: 久富崇、荒金尚子;et al
• 通讯作者: et al