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乳腺浸润性导管癌中 maspin 的表达分析及姜黄素对乳腺癌细胞系中其表达的调控。

Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines.

机构信息

Department of Anatomy, Vardhman Mahavir Medical College & Safdarjang Hospital, New Delhi, India.

出版信息

Chem Biol Interact. 2010 Feb 12;183(3):455-61. doi: 10.1016/j.cbi.2009.11.019. Epub 2009 Nov 26.

DOI:10.1016/j.cbi.2009.11.019
PMID:19944674
Abstract

In breast cancer, maspin, a serine protease inhibitor, can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. The clinical significance of maspin expression in breast cancer, especially in the sequence of ductal carcinoma in situ (DCIS)-invasive cancer-lymph node metastasis is well known in the Western countries, but its status in the rapidly increasing breast cancers in India remains unknown. The present study was designed to determine the clinical significance of maspin expression in invasive ductal carcinomas of breast (IDCs) in North Indian population and modulation of its expression by curcumin. Immunohistochemical analysis of maspin showed loss or reduced cytoplasmic expression in 36 of 59 (61%) tumors. Furthermore, breast cancer cells (MCF-7 (wild type p53) and MDA-MB-231 (mutant p53)) were treated with curcumin and the effect on expression of maspin gene at transcription and translation levels was analyzed by RT-PCR, immunofluorescence and Western blotting. Maspin expression was also correlated with p53 and Bcl-2 levels. Curcumin inhibited cell growth, induced apoptosis and upregulated maspin gene expression in MCF-7 cells and these findings were further correlated with the upregulation of p53 protein and downregulation of Bcl-2, suggesting maspin mediated apoptosis in MCF-7 cells. To our knowledge this is the first report showing the upregulation of maspin expression by curcumin in breast cancer cells and taken together with the clinical data suggests a potential therapeutic role for curcumin in inducing maspin mediated inhibition of invasion of breast carcinoma cells.

摘要

在乳腺癌中,丝氨酸蛋白酶抑制剂 maspin 可以在体内抑制肿瘤生长和转移,并在体外抑制肿瘤细胞的运动和侵袭。maspin 表达在乳腺癌中的临床意义,特别是在导管原位癌(DCIS)-浸润性癌-淋巴结转移的序列中,在西方国家是众所周知的,但它在印度迅速增加的乳腺癌中的地位尚不清楚。本研究旨在确定 maspin 在印度北部人群浸润性导管乳腺癌(IDCs)中的表达的临床意义,并研究姜黄素对其表达的调节。免疫组化分析显示,59 例肿瘤中有 36 例(61%)maspin 表达缺失或细胞质表达减少。此外,用姜黄素处理乳腺癌细胞(MCF-7(野生型 p53)和 MDA-MB-231(突变型 p53)),并通过 RT-PCR、免疫荧光和 Western blot 分析姜黄素对 maspin 基因转录和翻译水平表达的影响。还分析了 maspin 表达与 p53 和 Bcl-2 水平的相关性。姜黄素抑制 MCF-7 细胞的生长,诱导细胞凋亡,并上调 maspin 基因表达,这些发现与 p53 蛋白的上调和 Bcl-2 的下调进一步相关,提示 maspin 在 MCF-7 细胞中介导细胞凋亡。据我们所知,这是首次报道姜黄素在乳腺癌细胞中上调 maspin 表达的报告,与临床数据相结合表明姜黄素在诱导乳腺癌细胞侵袭抑制方面具有潜在的治疗作用。

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