研究动态
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应用网络药理学方法研究6-姜醇对宫颈癌的多靶点药理机制的整合。

Integrating network pharmacology approaches for the investigation of multi-target pharmacological mechanism of 6-shogaol against cervical cancer.

发表日期:2023 Mar 21
作者: Abdelbaset Mohamed Elasbali, Waleed Abu Al-Soud, Afnan Elayyan Mousa Elayyan, Ziad H Al-Oanzi, Hassan H Alhassan, Bashir M Mohamed, Hamad H Alanazi, Mohammad Saquib Ashraf, Shadman Moiz, Mitesh Patel, Mirav Patel, Mohd Adnan
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

传统的癌症治疗一直受到多种障碍的困扰,例如多药耐药、毒性和财务限制。相比之下,调节多种分子机制的植物化学物质在综合与替代医学中越来越受到关注。因此,本研究采用基于网络药理学的方法,探索了6-shogaol作为潜在治疗子宫颈癌(CC)的可能调控机制。在数据库(SuperPred、Targetnet、Swiss target prediction和PharmMapper)中筛选6-shogaol的靶基因信息,CC相关的靶基因从疾病数据库(DisGeNet和Genecards)和基因表达全志库中取得。采用STRING和Cytoscape生成蛋白质相互作用网络(PPI),利用拓扑分析和CytoNCA识别Hub基因。使用基因本体(GO)数据库Enrichr注释目标蛋白,利用基因与基因组百科全书(KEGG)数据库进行信号通路富集分析。基于Hub基因的分子对接和生存分析显示,有四个基因(HSP90AA1、HRAS、ESR1和EGFR)的结合能最低,大多数Hub基因(EGFR、SRC、CASP-3、HSP90AA1、MTOR、MAPK-1、MDM2和ESR1)与CC患者的总体生存相关联。总之,本研究提供了强有力的科学证据,支持使用6-shogoal作为治疗CC的细胞增殖、生长、迁移抑制剂和凋亡诱导剂,通过靶向参与CC生长的Hub基因。
Traditional treatment of cancer has been plagued by a number of obstacles, such as multiple drug resistance, toxicity and financial constraints. In contrast, phytochemicals that modulate a variety of molecular mechanisms are garnering increasing interest in complementary and alternative medicine. Therefore, an approach based on network pharmacology was used in the present study to explore possible regulatory mechanisms of 6-shogaol as a potential treatment for cervical cancer (CC). A number of public databases were screened to collect information on the target genes of 6-shogaol (SuperPred, Targetnet, Swiss target prediction and PharmMapper), while targets pertaining to CC were taken from disease databases (DisGeNet and Genecards) and gene expression omnibus (GEO) provided expression datasets. With STRING and Cytoscape, protein-protein interactions (PPI) were generated and topology analysis along with CytoNCA were used to identify the Hub genes. The Gene Ontology (GO) database Enrichr was used to annotate the target proteins, while, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, signaling pathway enrichment analysis was conducted. Molecular docking and survival analysis for the Hub genes revealed four genes (HSP90AA1, HRAS, ESR1 and EGFR) with lowest binding energy and majority of the Hub genes (EGFR, SRC, CASP-3, HSP90AA1, MTOR, MAPK-1, MDM2 and ESR1) were linked with the overall survival of CC patients. In conclusion, the present study provides the scientific evidence which strongly supports the use of 6-shogoal as an inhibitor of cellular proliferation, growth, migration as well as inducer of apoptosis via targeting the hub genes involved in the growth of CC.Communicated by Ramaswamy H. Sarma.