Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Vascular Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
BMC Complement Med Ther. 2023 Apr 17;23(1):122. doi: 10.1186/s12906-023-03938-5.
Osthole was traditionally used in treatment for various diseases. However, few studies had demonstrated that osthole could suppress bladder cancer cells and its mechanism was unclear. Therefore, we performed a research to explore the potential mechanism for osthole against bladder cancer.
Internet web servers SwissTargetPrediction, PharmMapper, SuperPRED, and TargetNet were used to predict the Osthole targets. GeneCards and the OMIM database were used to indicate bladder cancer targets. The intersection of two target gene fragments was used to obtain the key target genes. Protein-protein interaction (PPI) analysis was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Furthermore, we used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular function of target genes. AutoDock software was then used to perform molecular docking of target genes,osthole and co-crystal ligand. Finally, an in vitro experiment was conducted to validate bladder cancer inhibition by osthole.
Our analysis identified 369 intersection genes for osthole, the top ten target genes included MAPK1, AKT1, SRC, HRAS, HASP90AA1, PIK3R1, PTPN11, MAPK14, CREBBP, and RXRA. The GO and KEGG pathway enrichment results revealed that the PI3K-AKT pathway was closely correlated with osthole against bladder cancer. The osthole had cytotoxic effect on bladder cancer cells according to the cytotoxic assay. Additionally, osthole blocked the bladder cancer epithelial-mesenchymal transition and promoted bladder cancer cell apoptosis by inhibiting the PI3K-AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathways.
We found that osthole had cytotoxic effect on bladder cancer cells and inhibited invasion, migration, and epithelial-mesenchymal transition by inhibiting PI3K-AKT and JAK/STAT3 pathways in in vitro experiment. Above all, osthole might have potential significance in treatment of bladder cancer.
Bioinformatics, Computational Biology, Molecular Biology.
蛇床子素传统上用于治疗各种疾病。然而，很少有研究表明蛇床子素能够抑制膀胱癌细胞，其机制尚不清楚。因此，我们进行了一项研究，探索蛇床子素对抗膀胱癌的潜在机制。
使用互联网网络服务器 SwissTargetPrediction、PharmMapper、SuperPRED 和 TargetNet 预测蛇床子素的靶标。使用 GeneCards 和 OMIM 数据库指示膀胱癌靶标。通过交集两个靶基因片段获得关键靶基因。使用 Search Tool for the Retrieval of Interacting Genes (STRING) 数据库进行蛋白质-蛋白质相互作用 (PPI) 分析。此外，我们使用基因本体 (GO) 和京都基因与基因组百科全书 (KEGG) 通路富集分析来探讨靶基因的分子功能。然后使用 AutoDock 软件对靶基因、蛇床子素和共晶配体进行分子对接。最后，进行体外实验验证蛇床子素对膀胱癌的抑制作用。
我们的分析确定了 369 个蛇床子素的交集基因，前 10 个靶基因包括 MAPK1、AKT1、SRC、HRAS、HASP90AA1、PIK3R1、PTPN11、MAPK14、CREBBP 和 RXRA。GO 和 KEGG 通路富集结果表明，PI3K-AKT 通路与蛇床子素抑制膀胱癌密切相关。细胞毒性测定表明，蛇床子素对膀胱癌细胞具有细胞毒性作用。此外，蛇床子素通过抑制 PI3K-AKT 和 Janus 激酶/信号转导和转录激活因子 (JAK/STAT3) 通路，阻断膀胱癌上皮-间充质转化并促进膀胱癌细胞凋亡。
我们发现蛇床子素在体外实验中对膀胱癌细胞具有细胞毒性作用，并通过抑制 PI3K-AKT 和 JAK/STAT3 通路抑制侵袭、迁移和上皮-间充质转化。总之，蛇床子素在膀胱癌的治疗中可能具有潜在的意义。
生物信息学、计算生物学、分子生物学。
