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Molecular targeted drug discovery for cancer cell radiosensitization using RNA aptamars

使用 RNA 适体发现癌细胞放射增敏的分子靶向药物

基本信息

批准号：
20200039
负责人：
KURIMASA Akihiro
金额：
$ 20.22万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

It is well known that blocking protein kinases related to DNA repair machinery such as DNA-PKcs, ATM, or ATR enhance sensitivity to ionizing radiation (IR). From this point of view, we expect that tumor cell sensitivity against radiotherapy is enhanced by exploiting this mechanism. Protein kinases related to DNA repair machinery are activated by being phosphorylated. Therefore we attempted making the RNA engineering technology, and will develop new radiation sensitization medicine as a molecular target drug for cancer. In this experiment, we are making RNA aptamers against phosphorylated site of DNA-PKcs by SELEX. In this research, we produced RNA aptamers specific to DNA-PKcs phosphorylation site. Furtheremore their specific template sequences were analyzed by next-generation sequencing technology, and some that may recognize DNA-PKcs specifically were focused. U2OS cells are transfected with the RNA molecules, we tested whether can increase sensitivity of radiation. In conclusion, we found some RNA molecules that enhance sensitivity of radiation for U2OS cells.

众所周知，阻断与DNA修复机制（如DNA- pkcs、ATM或ATR）相关的蛋白激酶可增强对电离辐射（IR）的敏感性。从这个角度来看，我们期望通过利用这一机制来增强肿瘤细胞对放疗的敏感性。与DNA修复机制相关的蛋白激酶通过磷酸化被激活。因此，我们尝试制作RNA工程技术，并将开发新的放射增敏药物作为癌症的分子靶向药物。在本实验中，我们正在用SELEX制备针对DNA-PKcs磷酸化位点的RNA适配体。在本研究中，我们制备了DNA-PKcs磷酸化位点特异性的RNA适体。此外，利用新一代测序技术分析了它们的特异性模板序列，重点分析了一些可能特异性识别DNA-PKcs的模板序列。用RNA分子转染U2OS细胞，检测其是否能增加辐射敏感性。综上所述，我们发现一些RNA分子可以增强U2OS细胞的辐射敏感性。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

NK314 potentiates anti-tumor activity with adult T-cell leukemia-lymphoma cellsby inhibition of dual targets on topoisomerase II{alpha} and DNA-dependent protein kinase.

NK314 通过抑制拓扑异构酶 II{α} 和 DNA 依赖性蛋白激酶的双重靶标，增强成人 T 细胞白血病-淋巴瘤细胞的抗肿瘤活性。

DOI：
发表时间：
2011
期刊：
Blood
影响因子：
20.3
作者：
Yoshikawa M;Mukai Y;Okada Y;Yoshioka Y;Tsunoda S;Tsutsumi Y;Okada N;Aird WC;Doi T;Nakagawa S;Hisatomi T
通讯作者：
Hisatomi T

NK314 potentiates anti'tumor activity with adult T-cell leukemia-lymphoma cellsby inhibition of dual targets on topoisomerase II{alpha}c and DNA-dependent protein kinase.

NK314 通过抑制拓扑异构酶 II{α}c 和 DNA 依赖性蛋白激酶的双重靶标，增强成人 T 细胞白血病-淋巴瘤细胞的抗肿瘤活性。