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BJ-B11，一种热休克蛋白90（Hsp90）抑制剂，可抑制乳腺癌细胞的增殖和侵袭。

BJ-B11, an Hsp90 Inhibitor, Constrains the Proliferation and Invasion of Breast Cancer Cells.

作者信息

Liu Kaisheng, Chen Juan, Yang Fang, Zhou Zhifan, Liu Ying, Guo Yaomin, Hu Hong, Gao Hengyuan, Li Haili, Zhou Wenbin, Qin Bo, Wang Yifei

机构信息

Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen, China.

Shenzhen Nanshan District Shekou People's Hospital, Shenzhen, China.

出版信息

Front Oncol. 2019 Dec 18;9:1447. doi: 10.3389/fonc.2019.01447. eCollection 2019.

DOI:10.3389/fonc.2019.01447
PMID:31921692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6930179/
Abstract

Breast cancer is the leading cause of cancer-related deaths in women; however, its underlying etiology remains largely unknown. In this study, we systematically analyzed breast cancer tissues using comprehensive iTRAQ labeled quantitative proteomics, identifying 841 differentially expressed proteins (474 and 367 significantly over- and under-expressed, respectively), which were annotated by protein domain analysis. All the heat shock proteins identified were upregulated in breast cancer tissues; Hsp90 upregulation was also validated by RT-qPCR and immunohistochemistry, and high Hsp90 protein levels correlated with poorer survival. Hsp90AA1 overexpression promoted MDA-MB-231 cell proliferation, whilst BJ-B11, an Hsp90 inhibitor, hampered their invasion, migration, and proliferation in a time and dose-dependent manner and induced cell cycle arrest and apoptosis. BJ-B11 inhibited the expression of epithelial-mesenchymal transition (EMT) marker in MDA-MB-231 cells, whereas Hsp90AA1 promoted its expression. Moreover, BJ-B11 inhibited tumor growth in xenograft model. Altogether, Hsp90 activation is a risk factor in breast cancer patients, and BJ-B11 could be used to treat breast cancer.

摘要

乳腺癌是女性癌症相关死亡的主要原因；然而，其潜在病因在很大程度上仍不清楚。在本研究中，我们使用全面的iTRAQ标记定量蛋白质组学系统分析了乳腺癌组织，鉴定出841种差异表达蛋白（分别有474种和367种显著上调和下调），并通过蛋白质结构域分析对其进行了注释。在乳腺癌组织中鉴定出的所有热休克蛋白均上调；Hsp90的上调也通过RT-qPCR和免疫组织化学得到验证，并且高Hsp90蛋白水平与较差的生存率相关。Hsp90AA1的过表达促进了MDA-MB-231细胞的增殖，而Hsp90抑制剂BJ-B11以时间和剂量依赖的方式阻碍了它们的侵袭、迁移和增殖，并诱导细胞周期停滞和凋亡。BJ-B11抑制了MDA-MB-231细胞中上皮-间质转化（EMT）标志物的表达，而Hsp90AA1促进了其表达。此外，BJ-B11在异种移植模型中抑制了肿瘤生长。总之，Hsp90激活是乳腺癌患者的一个危险因素，BJ-B11可用于治疗乳腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/9d190d6bf9b5/fonc-09-01447-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/8bb3260eaedb/fonc-09-01447-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/30dee70bca66/fonc-09-01447-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/718aeca78ca2/fonc-09-01447-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/c5a7d3d0557a/fonc-09-01447-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/9d190d6bf9b5/fonc-09-01447-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/8bb3260eaedb/fonc-09-01447-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/30dee70bca66/fonc-09-01447-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/718aeca78ca2/fonc-09-01447-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/c5a7d3d0557a/fonc-09-01447-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bba/6930179/9d190d6bf9b5/fonc-09-01447-g0005.jpg

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