Midostaurin preferentially attenuates proliferation of triple-negative breast cancer cell lines through inhibition of Aurora kinase family.
Midostaurin preferentially attenuates proliferation of triple-negative breast cancer cell lines through inhibition of Aurora kinase family.
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DOI：
10.1186/s12929-015-0150-2
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发表时间：
2015-07-04
影响因子：
11
通讯作者：
Kikkawa U
中科院分区：
文献类型：
--
作者：
Kawai M;Nakashima A;Kamada S;Kikkawa U
根据激素受体和人表皮生长因子受体2等生物标志物受体的表达，乳腺癌分为三种亚型。三阴性乳腺癌（TNBC）不表达这些受体中的任何一种，并且具有预后不良的侵袭性表型，其对靶向激素受体和人表皮生长因子受体2的药物不敏感。因此，需要开发有效的治疗试剂来治疗TNBC。使用一组19种乳腺癌细胞系的研究表明，与非TNBC细胞相比，米多鲁肽（一种多靶点蛋白激酶抑制剂）优先抑制TNBC细胞的生长。一组癌细胞系的药物活性数据的聚类分析预测，米多替林与Aurora激酶抑制剂共享靶点。以下研究表明，米多替林减弱细胞中由Aurora激酶介导的磷酸化反应，并在体外直接抑制该蛋白激酶，并且该试剂诱导凋亡伴随TNBC细胞中4N和8N DNA细胞的积累。米多鲁肽可能通过抑制Aurora激酶家族来抑制乳腺癌细胞系中TNBC细胞的增殖。准确研究米多塞林对细胞生长的影响将有助于开发治疗TNBC的药物。本文的在线版本（doi：10.1186/s12929 - 015 - 0150 - 2）包含补充材料，可供授权用户使用。
Breast cancer is classified into three subtypes by the expression of biomarker receptors such as hormone receptors and human epidermal growth factor receptor 2. Triple-negative breast cancer (TNBC) expresses none of these receptors and has an aggressive phenotype with a poor prognosis, which is insensitive to the drugs that target the hormone receptors and human epidermal growth factor receptor 2. It is, thus, required to develop an effective therapeutic reagent to treat TNBC. The study using a panel of 19 breast cancer cell lines revealed that midostaurin, a multi-target protein kinase inhibitor, suppresses preferentially the growth of TNBC cells comparing with non-TNBC cells. Clustering analysis of the drug activity data for the panel of cancer cell lines predicted that midostaurin shares the target with Aurora kinase inhibitors. Following studies indicated that midostaurin attenuates the phosphorylation reaction mediated by Aurora kinase in the cells and directly inhibits this protein kinase in vitro, and that this reagent induces apoptosis accompanying accumulation of 4N and 8N DNA cells in TNBC cells. Midostaurin suppresses the proliferation of TNBC cells among the breast cancer cell lines presumably through the inhibition of the Aurora kinase family. The precise study of midostaurin on cell growth will contribute to the development of the drug for the treatment of TNBC. The online version of this article (doi:10.1186/s12929-015-0150-2) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.bbagrm.2010.09.004
发表时间：
2010-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
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通讯作者：
Sen S
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DOI：
10.1155/2014/357027
发表时间：
2014
期刊：
Chemotherapy research and practice
影响因子：
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作者：
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通讯作者：
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影响因子：
11
作者：
Nakashima A;Kawanishi I;Eguchi S;Yu EH;Eguchi S;Oshiro N;Yoshino K;Kikkawa U;Yonezawa K
通讯作者：
Yonezawa K
DOI：
10.1126/science.1236083
发表时间：
2013-11-22
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
14.9
作者：
Hung, Liang-Yi;Tseng, Joseph T.;Lee, Yi-Chao;Xia, Weiya;Wang, Ying-Nai;Wu, Min-Li;Chuang, Yu-Hsuan;Lai, Chein-Hsien;Chang, Wen-Chang
通讯作者：
Chang, Wen-Chang