2016年第43卷第7期目录
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封面故事:奥沙利铂(Oxaliplatin)被称为第三代铂类抗癌药物,但它的抗癌作用机制仍处在探索阶段.目前大多数的研究表明奥沙利铂的主要作用靶点是DNA分子,但它与DNA分子形成的关键结构和作用机制仍不明确.刘志国研究组运用紫外可见吸收光谱和原子力显微镜观察探索奥沙利铂与DNA在活体外的相互作用过程,揭示奥沙利铂产生抗癌作用的主要分子结构基础.封面图为单个质粒pUC19 DNA作用前以及与1 mmol/L奥沙利铂在37℃条件下避光作用4 h后在高定向热解石墨表面的单分子原子力显微镜成像.由图可见,奥沙利铂可导致质粒pUC19 DNA分子由伸展的环状转变为紧密的球状结构,此结构可能对奥沙利铂的抗癌活性和毒性产生重要影响.本研究从单分子水平上证实了奥沙利铂与DNA分子的作用过程.
(许凤杰,刘瑞斯,彪林海,祖元刚,刘志国.抗癌药物奥沙利铂与DNA分子相互作用的研究,本期第684~690页)
Cover Story:Oxaliplatin is a third-generation platinum derivative which is especially efficient for gastric and colorectal cancer treatment. Most studies revealed that the target of oxaliplatin is DNA molecule. However, the key structures formed by oxaliplatin and DNA still controversial so far. In this study, the interactions between oxaliplatin and DNA in vitro have been studied by UV spectra and atomic force microscopy (AFM) so as to reveal the structural basis of its anticancer activity. The structural characteristic after the incubation oxaliplatin at different concentrations with DNA for different time was investigated on freshly cleaved highly ordered pyrolytic graphite (HOPG) surface by atomic force microscopy (AFM). Based on the observed results, the interaction mechanism between oxaliplatin and DNA was proposed. High resolution AFM observation indicated that oxaliplatin can induce structural changes of pUC19 DNA from the extended chains to the intertangled structures with many nodes, and finally to a compact particle after 24 h incubation. The present results revealed that electrostatic and coordination interactions are important to condense plasmid DNA to a compact particle which may significantly influence the activity and cytotoxicity of oxaliplatin.
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综述与专论
研究快报
研究报告
技术与方法
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