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联合网络药理学和细胞学实验鉴定矢车菊素抗乳腺癌的潜在靶点及作用机制

Combined Network Pharmacology and Cytology Experiments to Identify Potential Anti-Breast Cancer Targets and Mechanisms of Delphinidin.

机构信息

Department of Pathology, Leshan People's Hospital, Leshan, China.

Department of Basic Medical Science, Chengdu Medical College, Chengdu, China.

出版信息

Nutr Cancer. 2022;74(7):2591-2606. doi: 10.1080/01635581.2021.2012582. Epub 2021 Dec 8.

DOI:10.1080/01635581.2021.2012582
PMID:34875956
Abstract

Delphinidin is a type of anthocyanin monomer with antioxidant, anti-inflammatory, and anti-tumor effects. However, the biological mechanisms underlying its anti-breast cancer activity have not been thoroughly studied. We further studied the effect of delphinidin on breast cancer cells through comprehensive network pharmacology, cellular and molecular experiments. We acquired the know therapeutic targets of delphinidin and obtained differentially expressed genes (DEGs) of breast cancer using RTCGA. We used topological analysis to screen out the 106 core targets of delphinium anti-breast cancer and performed functional analysis. These genes were mainly enriched in the pathways in cancer, Progesterone-mediated oocyte maturation and cell cycle. Then, by taking the intersection of the three analyzed data sets, important core targets (EGFR, TOP2A and PTGS2) were obtained and molecular-docking was performed to validate the result. Additionally, In Vitro experiments, MCF-7 and BT-474 cell proliferation was inhibited in a dose-dependent manner by delphinidin and the expressions of EGFR, TOP2A and PTGS were reduced. Moreover, delphinidin influenced cell cycle, the expressions of cdk1 and cyclin B1 were reduced. Furthermore, delphinidin induced apoptosis by activating the MAPK-Signaling pathway. Collectively, our findings suggested that delphinidin may offer effective approaches in breast cancer prevention and therapy.Supplemental data for this article is available online at http://dx.doi.org/10.1080/01635581.2021.2012582.

摘要

飞燕草素是一种具有抗氧化、抗炎和抗肿瘤作用的花色苷单体。然而,其抗乳腺癌活性的生物学机制尚未得到深入研究。我们通过综合网络药理学、细胞和分子实验进一步研究了飞燕草素对乳腺癌细胞的作用。我们获得了飞燕草素的治疗靶点,并使用 RTCGA 获得了乳腺癌的差异表达基因 (DEGs)。我们使用拓扑分析筛选出 106 个飞燕草抗乳腺癌的核心靶点,并进行了功能分析。这些基因主要富集在癌症途径、孕激素介导的卵母细胞成熟和细胞周期中。然后,通过取三个分析数据集的交集,得到重要的核心靶点 (EGFR、TOP2A 和 PTGS2),并进行分子对接验证结果。此外,体外实验表明,飞燕草素呈剂量依赖性抑制 MCF-7 和 BT-474 细胞增殖,降低 EGFR、TOP2A 和 PTGS 的表达。此外,飞燕草素通过激活 MAPK 信号通路影响细胞周期,降低 cdk1 和 cyclin B1 的表达。此外,飞燕草素通过激活 MAPK 信号通路诱导细胞凋亡。综上所述,我们的研究结果表明,飞燕草素可能为乳腺癌的预防和治疗提供有效的方法。本文的补充数据可在 http://dx.doi.org/10.1080/01635581.2021.2012582 在线获取。

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Combined Network Pharmacology and Cytology Experiments to Identify Potential Anti-Breast Cancer Targets and Mechanisms of Delphinidin.联合网络药理学和细胞学实验鉴定矢车菊素抗乳腺癌的潜在靶点及作用机制
Nutr Cancer. 2022;74(7):2591-2606. doi: 10.1080/01635581.2021.2012582. Epub 2021 Dec 8.
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Delphinidin reduces cell proliferation and induces apoptosis of non-small-cell lung cancer cells by targeting EGFR/VEGFR2 signaling pathways.飞燕草素通过靶向 EGFR/VEGFR2 信号通路减少非小细胞肺癌细胞的增殖并诱导其凋亡。
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Delphinidin induced protective autophagy via mTOR pathway suppression and AMPK pathway activation in HER-2 positive breast cancer cells.飞燕草素通过抑制 mTOR 通路和激活 AMPK 通路诱导 HER-2 阳性乳腺癌细胞的保护性自噬。
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Delphinidin induces cell cycle arrest and apoptosis in HER-2 positive breast cancer cell lines by regulating the NF-κB and MAPK signaling pathways.矢车菊素通过调节NF-κB和MAPK信号通路诱导HER-2阳性乳腺癌细胞系的细胞周期停滞和凋亡。
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[Delphinidin induces autophagy in HER-2+ breast cancer cells via inhibition of AKT/mTOR pathway].[矢车菊素通过抑制AKT/mTOR信号通路诱导HER-2+乳腺癌细胞发生自噬]
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Delphinidin suppresses proliferation and migration of human ovarian clear cell carcinoma cells through blocking AKT and ERK1/2 MAPK signaling pathways.飞燕草素通过阻断AKT和ERK1/2 MAPK信号通路抑制人卵巢透明细胞癌细胞的增殖和迁移。
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Delphinidin suppresses PMA-induced MMP-9 expression by blocking the NF-κB activation through MAPK signaling pathways in MCF-7 human breast carcinoma cells.飞燕草素通过阻断丝裂原活化蛋白激酶(MAPK)信号通路介导的核因子κB(NF-κB)激活,抑制佛波酯(PMA)诱导的MCF-7人乳腺癌细胞中基质金属蛋白酶-9(MMP-9)的表达。
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Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation.飞燕草素通过调节Met受体磷酸化来抑制细胞增殖和侵袭。
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Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables.飞燕草素(一种存在于有色水果和蔬菜中的花青素)对表皮生长因子受体信号通路的抑制作用
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Bioinformatics and network-based screening and discovery of potential molecular targets and small molecular drugs for breast cancer.基于生物信息学和网络的乳腺癌潜在分子靶点及小分子药物的筛选与发现
Front Pharmacol. 2022 Sep 20;13:942126. doi: 10.3389/fphar.2022.942126. eCollection 2022.