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.
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。