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在存在吸附于聚乙二醇的IgA的情况下,细胞内钙是MCF-7细胞凋亡调节的一个靶点。

Intracellular calcium is a target of modulation of apoptosis in MCF-7 cells in the presence of IgA adsorbed to polyethylene glycol.

作者信息

Honorio-França Adenilda Cristina, Nunes Gabriel Triches, Fagundes Danny Laura Gomes, de Marchi Patrícia Gelli Feres, Fernandes Rubian Trindade da Silva, França Juliana Luzia, França-Botelho Aline do Carmo, Moraes Lucélia Campelo Albuquerque, Varotti Fernando de Pilla, França Eduardo Luzía

机构信息

Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Garças, Mato Grosso, Brazil.

Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Garças, Mato Grosso, Brazil; Institute of Health Sciences, University Center of Planalto de Araxá, Araxá, Minas Gerais, Brazil.

出版信息

Onco Targets Ther. 2016 Feb 3;9:617-26. doi: 10.2147/OTT.S99839. eCollection 2016.

Abstract

PURPOSE

Clinical and epidemiological studies have indicated that breastfeeding has a protective effect on breast cancer risk. Protein-based drugs, including antibodies, are being developed to attain better forms of cancer therapy. Secretory IgA (SIgA) is the antibody class in human breast milk, and its activity can be linked to the protective effect of breastfeeding. The aim of this study was to investigate the effect of polyethylene glycol (PEG) microspheres with adsorbed SIgA on MCF-7 human breast cancer cells.

METHODS

The PEG microspheres were characterized by flow cytometry and fluorescence microscopy. The MCF-7 cells were obtained from American Type Culture Collection. MCF-7 cells were pre-incubated for 24 hours with or without SIgA (100 ng/mL), PEG microspheres or SIgA adsorbed in PEG microspheres (100 ng/mL). Viability, intracellular calcium release, and apoptosis in MCF-7 cells were determined by flow cytometry.

RESULTS

Fluorescence microscopy and flow cytometry analyses revealed that SIgA was able to adsorb to the PEG microspheres. The MCF-7 cells that were incubated with PEG microspheres with adsorbed SIgA showed decreased viability. MCF-7 cells that were incubated with SIgA or PEG microspheres with adsorbed SIgA had increased intracellular Ca(2+) levels. In the presence of SIgA, an increase in the percentage of apoptotic cells was observed. The highest apoptosis index was observed when the cells were treated with PEG microspheres with adsorbed SIgA.

CONCLUSION

These data suggest that colostral SIgA adsorbed to PEG microspheres has antitumor effects on human MCF-7 breast cancer cells and that the presence of large amounts of this protein in secreted breast milk may provide protection against breast tumors in women who breastfed.

摘要

目的

临床和流行病学研究表明,母乳喂养对乳腺癌风险具有保护作用。包括抗体在内的基于蛋白质的药物正在被开发以实现更好的癌症治疗形式。分泌型免疫球蛋白A(SIgA)是人类母乳中的抗体类别,其活性可能与母乳喂养的保护作用有关。本研究的目的是调查吸附有SIgA的聚乙二醇(PEG)微球对MCF-7人乳腺癌细胞的影响。

方法

通过流式细胞术和荧光显微镜对PEG微球进行表征。MCF-7细胞购自美国模式培养物集存库。MCF-7细胞在有或无SIgA(100 ng/mL)、PEG微球或吸附在PEG微球中的SIgA(100 ng/mL)的情况下预孵育24小时。通过流式细胞术测定MCF-7细胞的活力、细胞内钙释放和凋亡情况。

结果

荧光显微镜和流式细胞术分析表明,SIgA能够吸附到PEG微球上。与吸附有SIgA的PEG微球一起孵育的MCF-7细胞活力降低。与SIgA或吸附有SIgA的PEG微球一起孵育的MCF-7细胞细胞内Ca(2+)水平升高。在存在SIgA的情况下,观察到凋亡细胞百分比增加。当细胞用吸附有SIgA的PEG微球处理时,观察到最高的凋亡指数。

结论

这些数据表明,吸附到PEG微球上的初乳SIgA对人MCF-7乳腺癌细胞具有抗肿瘤作用,并且分泌的母乳中大量存在这种蛋白质可能为母乳喂养的女性提供针对乳腺肿瘤的保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f07/4745958/ea2c914f9cc9/ott-9-617Fig1.jpg

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