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用 CaCONPs 递送的凝集素处理 MCF-7 乳腺癌细胞系的蛋白质谱显示,分子伴侣、细胞骨架和膜相关蛋白发生变化。

Protein profile of MCF-7 breast cancer cell line treated with lectin delivered by CaCONPs revealed changes in molecular chaperones, cytoskeleton, and membrane-associated proteins.

机构信息

Department of Biology, College of Science, Baghdad University, Baghdad, Iraq; Department of Biomedical Engineering, College of Engineering, Al-Nahrain University, Baghdad, Iraq.

Department of Biology, College of Science, Baghdad University, Baghdad, Iraq.

出版信息

Int J Biol Macromol. 2021 Aug 1;184:636-647. doi: 10.1016/j.ijbiomac.2021.06.144. Epub 2021 Jun 24.

DOI:10.1016/j.ijbiomac.2021.06.144
PMID:34174302
Abstract

The second most predominant cancer in the world and the first among women is breast cancer. We aimed to study the protein abundance profiles induced by lectin purified from the Agaricus bisporus mushroom (ABL) and conjugated with CaCONPs in the MCF-7 breast cancer cell line. Two-dimensional electrophoresis (2-DE) and orbitrap mass spectrometry techniques were used to reveal the protein abundance pattern induced by lectin. Flow cytometric analysis showed the accumulation of ABL-CaCONPs treated cells in the G1 phase than the positive control. Thirteen proteins were found different in their abundance in breast cancer cells after 24 h exposure to lectin conjugated with CaCONPs. Most of the identified proteins were showing a low abundance in ABL-CaCONPs treated cells in comparison to the positive and negative controls, including V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP. Hornerin, tropomyosin alpha-1 chain, annexin A2, and protein disulfide-isomerase were up-regulated in comparison to the positive. Bioinformatic analyses revealed the regulation changes of these proteins mainly affected the pathways of 'Bcl-2-associated athanogene 2 signalling pathway', 'Unfolded protein response', 'Caveolar-mediated endocytosis signalling', 'Clathrin-mediated endocytosis signalling', 'Calcium signalling' and 'Sucrose degradation V', which are associated with breast cancer. We concluded that lectin altered the abundance in molecular chaperones/heat shock proteins, cytoskeletal, and metabolic proteins. Additionally, lectin induced a low abundance of MCF-7 cancer cell proteins in comparison to the positive and negative controls, including; V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP.

摘要

世界上第二大常见癌症,也是女性中第一大常见癌症是乳腺癌。我们旨在研究从双孢蘑菇(Agaricus bisporus)中纯化的凝集素与 CaCONPs 结合后在 MCF-7 乳腺癌细胞系中诱导的蛋白质丰度谱。二维电泳(2-DE)和轨道阱质谱技术用于揭示凝集素诱导的蛋白质丰度模式。流式细胞术分析显示,与阳性对照相比,ABL-CaCONPs 处理的细胞在 G1 期积累。在暴露于与 CaCONPs 结合的凝集素 24 小时后,在乳腺癌细胞中发现了 13 种蛋白质的丰度存在差异。与阳性和阴性对照相比,大多数鉴定出的蛋白质在 ABL-CaCONPs 处理的细胞中表达水平较低,包括 V -set 和免疫球蛋白结构域、血清白蛋白、肌动蛋白细胞质 1、磷酸丙糖异构酶、原肌球蛋白 alpha-4 链和内质网伴侣 BiP。与阳性对照相比,霍纳林、原肌球蛋白 alpha-1 链、膜联蛋白 A2 和蛋白质二硫键异构酶上调。生物信息学分析表明,这些蛋白质的调节变化主要影响“Bcl-2 相关抗凋亡基因 2 信号通路”、“未折叠蛋白反应”、“Caveolar 介导的内吞作用信号通路”、“网格蛋白介导的内吞作用信号通路”、“钙信号通路”和“蔗糖降解 V”途径,这些途径与乳腺癌相关。我们得出结论,凝集素改变了分子伴侣/热休克蛋白、细胞骨架和代谢蛋白的丰度。此外,与阳性和阴性对照相比,凝集素诱导 MCF-7 癌细胞蛋白质的丰度降低,包括 V -set 和免疫球蛋白结构域、血清白蛋白、肌动蛋白细胞质 1、磷酸丙糖异构酶、原肌球蛋白 alpha-4 链和内质网伴侣 BiP。

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