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阿司匹林诱导的 Bcl-2 易位及其在核内的磷酸化触发乳腺癌细胞凋亡。

Aspirin-induced Bcl-2 translocation and its phosphorylation in the nucleus trigger apoptosis in breast cancer cells.

机构信息

1] School of Biological Science, Nanyang Technological University, Singapore, Singapore [2] Pohang Center for Evaluation of Biomaterials, Pohang Technopark, Pohang, South Korea.

出版信息

Exp Mol Med. 2013 Oct 11;45(10):e47. doi: 10.1038/emm.2013.91.

DOI:10.1038/emm.2013.91
PMID:24113271
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3809363/
Abstract

Here, we report that B-cell lymphoma 2 (Bcl-2) is a novel target molecule of aspirin in breast cancer cells. Aspirin influenced the formation of a complex by Bcl-2 and FKBP38 and induced the nuclear translocation of Bcl-2 and its phosphorylation. These events inhibited cancer cell proliferation and subsequently enhanced MCF-7 breast cancer cell apoptosis. Bcl-2 knockdown using small interfering RNA (siRNA) delayed apoptotic cell death, which correlated with increased proliferation following aspirin exposure. In contrast, Bcl-2 overexpression enhanced the onset of aspirin-induced apoptosis, which was also associated with a significant increase in Bcl-2 phosphorylation in the nucleus. Therefore, this study may provide novel insight into the molecular mechanism of aspirin, particularly its anticancer effects in Bcl-2- and estrogen receptor-positive breast cancer cells.

摘要

在这里，我们报告 B 细胞淋巴瘤 2（Bcl-2）是阿司匹林在乳腺癌细胞中的一个新的靶分子。阿司匹林影响 Bcl-2 和 FKBP38 形成复合物，并诱导 Bcl-2 的核转位及其磷酸化。这些事件抑制了癌细胞的增殖，并随后增强 MCF-7 乳腺癌细胞的凋亡。使用小干扰 RNA（siRNA）敲低 Bcl-2 延迟了凋亡细胞死亡，这与阿司匹林暴露后增殖增加相关。相比之下，Bcl-2 的过表达增强了阿司匹林诱导的凋亡的发生，这也与核内 Bcl-2 磷酸化的显著增加相关。因此，本研究可能为阿司匹林的分子机制，特别是其在 Bcl-2 和雌激素受体阳性乳腺癌细胞中的抗癌作用提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/0c0de7a61c44/emm201391f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/cbf5c3d18fb7/emm201391f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/0c0de7a61c44/emm201391f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/cbf5c3d18fb7/emm201391f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/1cc7eaa62d56/emm201391f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/407e5e1f038a/emm201391f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/2e6792f18a5f/emm201391f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/846bcb0501b4/emm201391f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8954/3809363/0c0de7a61c44/emm201391f6.jpg

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An immunohistochemistry study of tissue bcl-2 expression and its serum levels in breast cancer patients.乳腺癌患者组织bcl-2表达及其血清水平的免疫组织化学研究。
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FKBP family proteins: immunophilins with versatile biological functions.FKBP家族蛋白：具有多种生物学功能的亲免素
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