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重组 MVL 诱导人肺癌细胞凋亡的蛋白质组学分析。

Proteomic analysis of apoptosis induction in human lung cancer cells by recombinant MVL.

机构信息

College of Light Industry and Food Sciences, South China University of Technology, 381 Wushan Road, Guangzhou, 510640, China.

出版信息

Amino Acids. 2011 Oct;41(4):923-32. doi: 10.1007/s00726-010-0791-0. Epub 2010 Nov 11.

Abstract

Lung cancer is still difficult to treat by current chemotherapeutic procedures. We recently found that MVL, an anti-HIV lectin from blue-green algae Microcystis viridis, also has antitumor activity. The objective of this study was to investigate apoptosis-inducing activity of recombinant MVL (R-MVL) and proteomic changes in A549 cells, and to identify the molecular pathways responsible for the anti-cancer action of R-MVL. We found that R-MVL induces A549 cells apoptosis in a dose-dependent manner by using MTT assay, fluorescent microscope (FM) and flow cytometry (FCM), and the IC50 was calculated to be 24.12 μg/ml. Subsequently, 7 altered proteins in R-MVL-treated A549 cells were identified, including upregulated aldehyde dehydrogenase 1 and β-actin, and five downregulated proteins: heat shock protein 90, heat shock 60, plastin 3, tropomyosin 3, and β-tubulin. Further bioinformatics analysis predicted the potential pathways for R-MVL to induce apoptosis of A549 cells. In conclusion, this is the first report to investigate anti-cancer activity of R-MVL and its mechanism of action by proteomics analysis. Our observations provide potential therapeutic targets for lung cancer inhibitor intervention and implicated the development of novel anti-cancer therapeutic strategies.

摘要

目前的化疗程序仍然难以治疗肺癌。我们最近发现,来自蓝绿藻微囊藻的抗 HIV 凝集素 MVL 也具有抗肿瘤活性。本研究的目的是研究重组 MVL(R-MVL)诱导 A549 细胞凋亡的活性和蛋白质组变化,并确定 R-MVL 抗癌作用的分子途径。我们发现 R-MVL 通过 MTT 测定、荧光显微镜(FM)和流式细胞术(FCM)以剂量依赖的方式诱导 A549 细胞凋亡,IC50 计算为 24.12μg/ml。随后,在 R-MVL 处理的 A549 细胞中鉴定出 7 种改变的蛋白质,包括上调的醛脱氢酶 1 和 β-肌动蛋白,以及 5 种下调的蛋白质:热休克蛋白 90、热休克 60、肌动蛋白结合蛋白 3、原肌球蛋白 3 和β-微管蛋白。进一步的生物信息学分析预测了 R-MVL 诱导 A549 细胞凋亡的潜在途径。总之,这是首次通过蛋白质组学分析研究 R-MVL 的抗癌活性及其作用机制。我们的观察结果为肺癌抑制剂干预提供了潜在的治疗靶点,并暗示了新的抗癌治疗策略的发展。

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