背景:非小细胞肺癌(NSCLC)患者易患2019年冠状病毒病(COVID-19),但目前的治疗方法有限。淫羊藿苷II(IS),一种来自植物淫羊藿苷的类黄酮化合物,显示抗癌,抗炎和免疫调节作用。本研究旨在评估IS对患有COVID-19(NSCLC/COVID-19)的NSCLC患者的可能影响和潜在机制。
方法:NSCLC/COVID-19靶标被定义为NSCLC(从癌症基因组图谱数据库收集)和COVID-19靶标(从基因卡的疾病数据库收集,OMIM,和NCBI)。使用生存R包分析NSCLC/COVID-19靶点与NSCLC患者生存率的相关性。使用单变量和多变量Cox比例风险回归模型进行预后分析。此外,IS治疗NSCLC/COVID-19的靶点被定义为IS的重叠靶点(从TMSCP药物数据库预测,HERB,SwissTarget预测)和非小细胞肺癌/COVID-19目标。基因本体论和京都百科全书基因和基因组富集分析这些治疗目标的目的是了解生物过程,细胞成分,分子功能和信号通路。通过蛋白质-蛋白质相互作用网络分析枢纽靶标,并通过分子对接表征与IS的结合能力。
结果:在NSCLC/COVID-19治疗中,IS的中心靶点包括F2,SELE,MMP1、MMP2、AGTR1和AGTR2的分子对接结果表明,上述靶蛋白与IS具有良好的结合度。网络药理学表明,IS可能会影响白细胞的迁移,炎症反应和活性氧代谢过程,以及调节NSCLC/COVID-19中白细胞介素-17、肿瘤坏死因子和缺氧诱导因子-1信号通路。
结论:IS可能会提高目前临床抗炎和抗癌治疗的疗效,使合并COVID-19的NSCLC患者受益。
BACKGROUND: Patients with non-small cell lung cancer (NSCLC) are susceptible to coronavirus disease-2019 (COVID-19), but current treatments are limited. Icariside II (IS), a flavonoid compound derived from the plant epimedin, showed anti-cancer,anti-inflammation and immunoregulation effects. The present study aimed to evaluate the possible effect and underlying mechanisms of IS on NSCLC patients with COVID-19 (NSCLC/COVID-19).
METHODS: NSCLC/COVID-19 targets were defined as the common targets of NSCLC (collected from The Cancer Genome Atlas database) and COVID-19 targets (collected from disease database of Genecards, OMIM, and NCBI). The correlations of NSCLC/COVID-19 targets and survival rates in patients with NSCLC were analyzed using the survival R package. Prognostic analyses were performed using univariate and multivariate Cox proportional hazards regression models. Furthermore, the targets in IS treatment of NSCLC/COVID-19 were defined as the overlapping targets of IS (predicted from drug database of TMSCP, HERBs, SwissTarget Prediction) and NSCLC/COVID-19 targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of these treatment targets were performed aiming to understand the biological process, cellular component, molecular function and signaling pathway. The hub targets were analyzed by a protein-protein interaction network and the binding capacity with IS was characterized by molecular docking.
RESULTS: The hub targets for IS in the treatment of NSCLC/COVID-19 includes F2, SELE, MMP1, MMP2, AGTR1 and AGTR2, and the molecular docking results showed that the above target proteins had a good binding degree to IS. Network pharmacology showed that IS might affect the leucocytes migration, inflammation response and active oxygen species metabolic process, as well as regulate the interleukin-17, tumor necrosus factor and hypoxia-inducible factor-1 signaling pathway in NSCLC/COVID-19.
CONCLUSIONS: IS may enhance the therapeutic efficacy of current clinical anti-inflammatory and anti-cancer therapy to benefit patients with NSCLC combined with COVID-19.