Quantitative proteomic analysis of human lung tumor xenografts treated with the ectopic ATP synthase inhibitor citreoviridin.
Quantitative proteomic analysis of human lung tumor xenografts treated with the ectopic ATP synthase inhibitor citreoviridin.
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DOI：
10.1371/journal.pone.0070642
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Juan HF
中科院分区：
文献类型：
--
作者：
Wu YH;Hu CW;Chien CW;Chen YJ;Huang HC;Juan HF
ATP合酶存在于几种类型的癌细胞的质膜上。黄绿青霉素是一种ATP合成酶抑制剂，选择性抑制肺癌的增殖和生长，而不影响正常细胞。然而，在体内靶向异位ATP合酶的整体效果还没有得到很好的定义。在这项研究中，我们进行了定量蛋白质组学分析，使用同量异序标签的相对和绝对定量（iTRAQ），并提供了一个全面的了解，在肺癌异种移植模型的复杂的调节黄绿青霉素。由于定量的高重现性，我们获得了定量蛋白质组学分析，鉴定了2，659种蛋白质。通过对141个差异表达蛋白的生物信息学分析发现，黄绿青霉素可诱导肺癌中葡萄糖代谢相关酶表达的改变。黄绿青霉素对葡萄糖代谢和储存相关酶的上调作用表明，黄绿青霉素可减少大分子合成的糖酵解中间产物，抑制细胞增殖。使用全面的蛋白质组学，结果确定了代谢方面，有助于解释黄绿青霉素在肺癌中的抗肿瘤作用，这可能会导致更好地理解癌症治疗中代谢和肿瘤发生之间的联系。
ATP synthase is present on the plasma membrane of several types of cancer cells. Citreoviridin, an ATP synthase inhibitor, selectively suppresses the proliferation and growth of lung cancer without affecting normal cells. However, the global effects of targeting ectopic ATP synthase in vivo have not been well defined. In this study, we performed quantitative proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) and provided a comprehensive insight into the complicated regulation by citreoviridin in a lung cancer xenograft model. With high reproducibility of the quantitation, we obtained quantitative proteomic profiling with 2,659 proteins identified. Bioinformatics analysis of the 141 differentially expressed proteins selected by their relative abundance revealed that citreoviridin induces alterations in the expression of glucose metabolism-related enzymes in lung cancer. The up-regulation of enzymes involved in gluconeogenesis and storage of glucose indicated that citreoviridin may reduce the glycolytic intermediates for macromolecule synthesis and inhibit cell proliferation. Using comprehensive proteomics, the results identify metabolic aspects that help explain the antitumorigenic effect of citreoviridin in lung cancer, which may lead to a better understanding of the links between metabolism and tumorigenesis in cancer therapy.
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DOI：
10.1111/j.1749-6632.1974.tb14440.x
发表时间：
1974-01-01
影响因子：
5.2
作者：
GOLD, J
通讯作者：
GOLD, J
影响因子：
7
作者：
Han, Chia-Li;Chien, Chih-Wei;Chen, Yu-Ju
通讯作者：
Chen, Yu-Ju
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.
影响因子：
11.2
作者：
Chang, Hsin-Yi;Huang, Hsuan-Cheng;Juan, Hsueh-Fen
通讯作者：
Juan, Hsueh-Fen