Department of Pathology, Leshan People's Hospital, Leshan, China.
Department of Basic Medical Science, Chengdu Medical College, Chengdu, China.
Nutr Cancer. 2022;74(7):2591-2606. doi: 10.1080/01635581.2021.2012582. Epub 2021 Dec 8.
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.
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。