Element array by scanning X-ray fluorescence microscopy after Cis-diamminedichloro-platinum(II) treatment
Element array by scanning X-ray fluorescence microscopy after Cis-diamminedichloro-platinum(II) treatment
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DOI：
10.1158/0008-5472.can-05-0373
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发表时间：
2005-06-15
期刊：
影响因子：
11.2
通讯作者：
Ishikawa, T
中科院分区：
文献类型：
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作者：
Shimura, M;Saito, A;Ishikawa, T
矿物质对细胞功能非常重要，如转录和酶活性，也参与抗癌化疗化合物的新陈代谢。分析单个细胞的胞内成分有助于了解肿瘤耐药的机制，并可能为抗癌化疗提供新的策略。利用最近发展的扫描X射线荧光显微镜(SXFM)技术，我们分析了顺式二氨基二氯铂(CDDP)处理后的细胞内元素，CDDP是一种基于铂的抗癌剂。SXFM(元素阵列)的图像显示，耐药细胞的平均铂含量比敏感细胞少2.6倍，锌含量与细胞内铂含量呈负相关。数据表明，锌相关的解毒作用是导致对顺铂产生耐药性的原因。在与锌相关的排泄因子中，谷胱甘肽与锌的含量高度相关。CDDP和锌(II)螯合剂的联合处理导致三倍以上的铂被掺入，伴随而来的是谷胱甘肽的下调。我们认为，SXFM产生的元件阵列为癌症生物学和治疗开辟了新的途径。
Minerals are important for cellular functions, such as transcription and enzyme activity, and are also involved in the metabolism of anticancer chemotherapeutic compounds. Profiling of intracellular elements in individual cells could help in understanding the mechanism of drug resistance in tumors and possibly provide a new strategy of anticancer chemotherapy. Using a recently developed technique of scanning X-ray fluorescence microscopy (SXFM), we analyzed intracellular elements after treatment with cis-diamminedichloro-platinum(II) (CDDP), a platinum-based anticancer agent. The images obtained by SXFM (element array) revealed that the average Pt content of CDDP-resistant cells was 2.6 times less than that of sensitive cells, and the zinc content was inversely correlated with the intracellular Pt content. Data suggested that Zn-related detoxification is responsible for resistance to CDDP. Of Zn-related excretion factors, glutathione was highly correlated with the amount of Zn. The combined treatment of CDDP and a Zn(II) chelator resulted in the incorporation of thrice more Pt with the concomitant down-regulation of glutathione. We propose that the generation of an element array by SXFM opens up new avenues in cancer biology and treatment.