背景:乳腺癌是最常见的女性恶性肿瘤之一。本研究探讨了两种植物化合物(BrucaineD和Narclasine)抑制乳腺癌细胞增殖的潜在机制。
目的:本研究的目的是探讨布鲁卡因D和Narclasine对乳腺癌发展的影响及其潜在的药物靶点。
方法:GSE85871数据集包含212个样本和标志基因集。all.v2023.1.Hs.符号。gmt\"是从基因表达综合(GEO)数据库和分子特征数据库(MSigDB)数据库下载的,分别。应用主成分分析(PCA)对显示相似基因表达模式的簇进行分类。使用单样品基因集富集分析(ssGSEA)来计算不同药物治疗组的标志评分。血管生成相关基因的表达,检测糖酵解和细胞周期。进行蛋白质-蛋白质相互作用(PPI)网络分析以研究hub基因的相互作用。然后,HERB数据库用于鉴定Narclasine和BruceineD的潜在靶基因。最后,进行了体外实验以验证部分药物-靶标对。
结果:PCA分析表明,在6种药物治疗组中发生了基因表达模式的显着变化(Narciclasine,BruceineD,JaponiconeA,1β-羟基丙氨酸内酯,不列颠宁,和四种混合药物)与其余药物治疗组相比。ssGSEA途径富集分析表明,Narciclasine和Bruceine处理具有相似的富集途径,例如,抑制与血管生成相关的途径,糖酵解,和细胞周期,等。.进一步的基因表达分析证实,Narciclasine和Bruceine具有很强的抑制这些细胞周期基因的能力,还有MYC,CHEK2,MELK,在PPI分析中,CDK4和EZH2彼此紧密地相互作用。药物靶标预测显示雄激素受体(AR)和雌激素受体1(ESR1)是BruceineD的靶标,细胞色素P4503A4酶(CYP3A4)是Narciclasine的靶标。细胞实验还证实了Narciclasine和CYP3A4之间的连接。
结论:本研究揭示了Narciclasine和BruceineD可以抑制乳腺癌的生长,并预测了这两种药物的潜在靶标。为乳腺癌患者提供了新的治疗方向。
BACKGROUND: Breast cancer is one of the most common female malignancies. This study explored the underlying mechanism through which the two plant compounds (Brucaine D and Narclasine) inhibited the proliferation of breast cancer cells.
OBJECTIVE: The purpose of this study was to explore the effect of Brucaine D and Narclasine on breast cancer development and their potential drug targets.
METHODS: GSE85871 dataset containing 212 samples and the hallmark gene set \"h.all.v2023.1.Hs.symbols.gmt\" were downloaded from the Gene Expression Omnibus (GEO) database and the Molecular Signatures Database (MSigDB) database, respectively. Principal component analysis (PCA) was applied to classify clusters showing similar gene expression pattern. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the hallmark score for different drug treatment groups. The expressions of genes related to angiogenesis, glycolysis and cell cycle were detected. Protein-protein interaction (PPI) network analysis was performed to study the interaction of the hub genes. Then, HERB database was employed to identify potential target genes for Narclasine and Bruceine D. Finally, in vitro experiments were conducted to validate partial drug-target pair.
RESULTS: PCA analysis showed that the significant changes in gene expression patterns took place in 6 drugs treatment groups (Narciclasine, Bruceine D, Japonicone A, 1beta-hydroxyalatolactone, Britanin, and four mixture drugs) in comparison to the remaining drug treatment groups. The ssGSEA pathway enrichment analysis demonstrated that Narciclasine and Bruceine treatments had similar enriched pathways, for instance, suppressed pathways related to angiogenesis, Glycolysis, and cell cycle, etc.. Further gene expression analysis confirmed that Narciclasine and Bruceine had a strong ability to inhibit these cell cycle genes, and that MYC, CHEK2, MELK, CDK4 and EZH2 were closely interacted with each other in the PPI analysis. Drug target prediction revealed that Androgen Receptor (AR) and Estrogen Receptor 1 (ESR1) were the targets for Bruceine D, and Cytochrome P450 3A4 enzyme (CYP3A4) was the target for Narciclasine. Cell experiments also confirmed the connections between Narciclasine and CYP3A4.
CONCLUSIONS: The present study uncovered that Narciclasine and Bruceine D could inhibit the growth of breast cancer and also predicted the potential targets for these two drugs, providing a new therapeutic direction for breast cancer patients.