Schisandra chinensis Bee Pollen Extract Inhibits Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells via Ferroptosis-, Wnt-, and Focal Adhesion–Signaling Pathways

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2024-07-02 DOI:10.2147/dddt.s461581

Zhiliang Li, Jiali Yang, Yang Sun, Shuo Han, Jietao Gong, Yi Zhang, Zhiyuan Feng, Hong Yao, Peiying Shi

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Abstract

Purpose: Bee pollen possesses favorable anticancer activities. As a medicinal plant source, Schisandra chinensis bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti–liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells.
Methods: The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR.
Results: Tandem mass tag-based quantitative proteomics showed that 61 differentially expressed proteins were obtained in the SCBPE group compared with the negative-control group: 18 significantly downregulated and 43 significantly upregulated proteins. Bioinformatic analysis showed the significantly enriched KEGG pathways were predominantly ferroptosis-, Wnt-, and hepatocellular carcinoma-signaling ones. Protein–protein interaction network analysis and RT-qPCR validation revealed SCBPE also downregulated the focal adhesion–signaling pathway, which is abrogated by PF-562271, a well-known inhibitor of FAK.
Conclusion: This study confirmed SCBPE suppressed the cell proliferation and migration of hepatocellular carcinoma HepG2 cells, mainly through modulation of ferroptosis-, Wnt-, hepatocellular carcinoma-, and focal adhesion–signaling pathways, providing scientific data supporting adjuvant treatment of hepatocellular carcinoma using SCBP.

Keywords: Schisandra chinensis bee pollen extract, HepG2 cells, proteomics, ferroptosis, Wnt-signaling pathway, focal adhesion–signaling pathway

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五味子花粉提取物通过铁凋亡、Wnt 和病灶粘附信号通路抑制肝细胞癌 HepG2 细胞的增殖和迁移

目的：蜂花粉具有良好的抗癌活性。作为一种药用植物来源，五味子蜂花粉（SCBP）具有潜在的药理特性，如降低顺铂诱导的肝损伤，但其抗肝癌作用仍鲜有报道。本文旨在研究SCBP提取物（SCBPE）对肝癌HepG2细胞的作用及其机制：方法：SCBPE 对 HepG2 细胞增殖和迁移的影响通过 MTT 试验、形态学观察或划痕试验进行评估。此外，还采用了基于串联质量标签的定量蛋白质组学研究其影响机制。通过 RT-qPCR 验证了已鉴定蛋白质的 mRNA 表达水平：结果：基于串联质量标签的定量蛋白质组学显示，与阴性对照组相比，SCBPE 组获得了 61 个差异表达的蛋白质，其中 18 个显著下调，43 个显著上调：结果：基于串联质量标签的定量蛋白质组学显示，与阴性对照组相比，SCBPE 组有 61 个差异表达蛋白质：18 个明显下调，43 个明显上调。生物信息学分析表明，显著富集的 KEGG 通路主要是铁突变、Wnt 和肝细胞癌信号通路。蛋白质-蛋白质相互作用网络分析和 RT-qPCR 验证显示，SCBPE 还下调了病灶粘附信号通路，而 PF-562271 （一种著名的 FAK 抑制剂）则可减轻这种下调作用：本研究证实SCBPE主要通过调控铁突变、Wnt、肝癌和局灶粘附信号通路抑制肝癌HepG2细胞的增殖和迁移，为利用SCBP辅助治疗肝癌提供了科学数据支持。关键词：五味子蜂花粉五味子花粉提取物 HepG2 细胞蛋白质组学铁突变 Wnt 信号通路局灶粘附信号通路

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.