PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：神经母细胞瘤，儿童中普遍存在的实体瘤，通常表现为隐藏的发作部位，快速增长,和高转移潜力。高危神经母细胞瘤患儿的预后仍然很差，强调迫切需要新的预后模型和治疗途径。近年来,葛根素,作为一种从中药葛根中提取的小分子药物，已证明对各种癌细胞类型具有显著的抗癌作用。在这项研究中,通过生物信息学分析和体外实验，研究了葛根素治疗神经母细胞瘤的潜力和机制，并建立了预后模型。
方法：通过构建药物靶标和疾病基因数据库，共观察9个药物-疾病相关靶标。此外,进行GO和KEGG富集分析以探索其治疗效果的潜在机制。为了构建预后模型，进行风险回归分析和LASSO分析进行验证。最后,确定了预后基因。进行降落伞试验和免疫荧光染色以验证葛根素在神经母细胞瘤治疗中的潜在机制。
结果：三个预后基因，即，鉴定了BIRC5、TIMP2和CASP9。体外研究证实葛根素对BIRC5、TIMP2和CASP9表达的影响，抑制神经母细胞瘤SH-SY5Y细胞的增殖。葛根素破坏细胞骨架,促进间隙连接沟通，减少入侵和迁移，并诱导SH-SY5Y细胞线粒体损伤。
结论：基于网络药理学和生物信息学分析，结合体外实验验证,由此观察到葛根素增强神经母细胞瘤的GJIC，破坏细胞骨架，从而抑制细胞侵袭和迁移，导致肿瘤细胞的线粒体损伤，并抑制细胞增殖。总的来说,葛根素,作为一种天然的药用化合物，确实有可能作为神经母细胞瘤的新疗法。
方法：通过构建药物靶标和疾病基因数据库，共观察9个药物-疾病相关靶标。此外,进行GO和KEGG富集分析以探索其治疗效果的潜在机制。为了构建预后模型，进行风险回归分析和LASSO分析进行验证。最后,确定了预后基因。进行降落伞试验和免疫荧光染色以验证葛根素在神经母细胞瘤治疗中的潜在机制。
结果：三个预后基因，即，鉴定了BIRC5、TIMP2和CASP9。体外研究证实葛根素对BIRC5、TIMP2和CASP9表达的影响，抑制神经母细胞瘤SH-SY5Y细胞的增殖。葛根素破坏细胞骨架,促进间隙连接沟通，减少入侵和迁移，并诱导SH-SY5Y细胞线粒体损伤。
结论：基于网络药理学和生物信息学分析，结合体外实验验证,由此观察到葛根素增强神经母细胞瘤的GJIC，破坏细胞骨架，从而抑制细胞侵袭和迁移，导致肿瘤细胞的线粒体损伤，并抑制细胞增殖。总的来说,葛根素,作为一种天然的药用化合物，确实有可能作为神经母细胞瘤的新疗法。
