葛根素抗神经母细胞瘤的作用和机制:来自生物信息学和体外实验的见解。
Effects and mechanisms of puerarin against neuroblastoma: insights from bioinformatics and in vitro experiments.
发表日期:2024 Jul 09
作者:
Xiaohui Sui, Tingting Liu, Zhiyun Zou, Baoqing Zhang, Guiju Zhang
来源:
Disease Models & Mechanisms
摘要:
神经母细胞瘤是儿童常见的实体瘤,常表现为发病部位隐蔽、生长迅速、转移潜力高。高危神经母细胞瘤儿童的预后仍然很差,凸显了对新的预后模型和治疗途径的迫切需要。近年来,葛根素作为从中药葛根中提取的小分子药物,对多种癌细胞具有显着的抗癌作用。本研究通过生物信息学分析和体外实验,探讨葛根素治疗神经母细胞瘤的潜力和机制,并建立预后模型。通过构建药物数据库,观察了9个药物与疾病相关的靶点。目标和疾病基因。此外,还进行GO和KEGG富集分析,探讨其治疗作用的潜在机制。为了构建预后模型,进行了风险回归分析和LASSO分析进行验证。最后,确定了预后基因。通过降落伞试验和免疫荧光染色验证葛根素治疗神经母细胞瘤的潜在机制。鉴定出 BIRC5、TIMP2 和 CASP9 三个预后基因。体外研究验证了葛根素对 BIRC5、TIMP2 和 CASP9 表达的影响,抑制神经母细胞瘤 SH-SY5Y 细胞的增殖。葛根素破坏SH-SY5Y细胞的细胞骨架,促进间隙连接通讯,减少侵袭和迁移,并诱导线粒体损伤。基于网络药理学和生物信息学分析,结合体外实验验证,观察葛根素可增强神经母细胞瘤中的GJIC,破坏细胞骨架从而抑制细胞侵袭和迁移,引起肿瘤细胞线粒体损伤,抑制细胞增殖。总体而言,葛根素作为一种天然药物化合物,确实具有作为神经母细胞瘤新疗法的潜力。© 2024。作者。
Neuroblastoma, a prevalent solid tumor in children, often manifests with hidden onset sites, rapid growth, and high metastatic potential. The prognosis for children with high-risk neuroblastoma remains poor, highlighting the urgent need for novel prognostic models and therapeutic avenues. In recent years, puerarin, as a kind of small molecule drug extracted from Chinese medicine Pueraria lobata, has demonstrated significant anticancer effects on various cancer cell types. In this study, through bioinformatics analysis and in vitro experiments, the potential and mechanism of puerarin in the treatment of neuroblastoma were investigated, and a prognostic model was established.A total of 9 drug-disease related targets were observed by constructing a database of drug targets and disease genes. Besides, GO and KEGG enrichment analysis was performed to explore the potential mechanism of its therapeutic effect. To construct the prognostic model, risk regression analysis and LASSO analysis were carried out for validation. Finally, the prognostic genes were identified. Parachute test and immunofluorescence staining were performed to verify the potential mechanism of puerarin in neuroblastoma treatment.Three prognostic genes, i.e., BIRC5, TIMP2 and CASP9, were identified. In vitro studies verified puerarin's impact on BIRC5, TIMP2, and CASP9 expression, inhibiting proliferation in neuroblastoma SH-SY5Y cells. Puerarin disrupts the cytoskeleton, boosts gap junctional communication, curtailing invasion and migration, and induces mitochondrial damage in SH-SY5Y cells.Based on network pharmacology and bioinformatics analysis, combined with in vitro experimental verification, puerarin was hereby observed to enhance GJIC in neuroblastoma, destroy cytoskeleton and thus inhibit cell invasion and migration, cause mitochondrial damage of tumor cells, and inhibit cell proliferation. Overall, puerarin, as a natural medicinal compound, does hold potential as a novel therapy for neuroblastoma.© 2024. The Author(s).