摘要
目的采用网络药理学、分子对接技术和细胞实验,探讨盐酸药根碱(JH)对人骨肉瘤细胞(HOS)的潜在作用靶点和对细胞的增殖、迁移、侵袭的影响及作用机制。方法首先通过数据库筛选JH的成分靶点,HOS相关的疾病靶点,以此来构建药物-靶点-疾病可视化网络和蛋白相互作用网络(PPI),然后进行GO和KEGG富集分析,采用分子对接软件对潜在的作用靶点(靶点数目最多的活性成分和蛋白相互作用中自由度最大的蛋白质)进行验证。采用不同浓度的JH处理HOS,通过MTT测定、平板克隆形成、Transwell小室侵袭与迁移实验证实JH在HOS细胞增殖中的抑制作用。结果该研究共获得JH抗HOS的靶点共有26个,富集分析提示JH通过多种信号途径发挥抗HOS的作用;分子对接显示JH与主要靶点之间具有良好的结合活性;与对照组相比,JH能显著降低HOS细胞活性;与对照组相比,JH组细胞的增殖、迁移能力显著降低。结论JH可能通过多种靶点有效抑制HOS增殖。经体外细胞实验验证表明,JH随着浓度增加,可抑制HOS的增殖、侵袭和迁移。因此,可能是一种有效的潜在抗HOS药物。
Objective To investigate the potential targets of jatrorrhizine hydrochloride(JH)on human osteosarcoma cells(HOS)and its effects on cell proliferation,migration,invasion and mechanism of action based on network pharmacology,molecular docking techniques and cellular assays.Methods Firstly,the constituent targets of JH and HOS-related disease targets were screened through the database,and as a way to construct and map the drug-target-disease visualization network and protein interaction network(PPI)and perform GO and KEGG enrichment analysis.And then the validation of potential targets of action(active ingredients with the highest number of targets and proteins with the highest degree of freedom in protein interactions)was performed by used molecular docking software.HOS cells were treated with different concentrations of JH,and the inhibitory effect of JH on the proliferation of HOS was confirmed by MTT assay,plate clone formation,and Transwell invasion and migration assay.Results In this study,a total of 26 anti-osteosarcoma targets of JH were obtained,and the enrichment analysis suggested that JH exerted its anti-osteosarcoma effects through various signaling pathways.The molecular docking showed good binding activity between JH and the main targets.Compared with the blank group,JH significantly reduced the activity,proliferation and migration ability of HOS.Conclusion JH might effectively inhibit HOS proliferation through multiple targets.In vitro cellular assays showed that JH could inhibite the proliferation,invasion and migration of HOS with the increasing of concentrations,and therefore might be as an effective potential anti-osteosarcoma drug.
作者
赵冰洁
阮英
宁志丰
ZHAO Bing-jie;RUAN Ying;NING Zhi-feng(School of Pharmacy,Xianning Medical College,Hubei University of Science and Technoligy,Xianning Hubei 437100,China)
出处
《湖北科技学院学报（医学版）》
2023年第6期499-505,共7页
Journal of Hubei University of Science and Technology(Medical Sciences)
基金
湖北科技学院五官专项(202002)
湖北省重点研发计划大健康专项(2022BCE011)。
关键词
盐酸药根碱
人骨肉瘤
增殖
网络药理学
分子对接
Jatrorrhizine hydrochloride
Human osteosarcoma
Proliferation
Network pharmacology
Molecular docking
