Abstract：
This study investigated mogrol\'s impact on non-small cell lung cancer (NSCLC) radiosensitivity and underlying mechanisms, using various methods including assays, bioinformatics, and xenograft models. CCK-8, clonogenic, flow cytometry, TUNEL, and Western blot assays evaluated mogrol and radiation effects on NSCLC viability and apoptosis. Ubiquitin-specific protease 22 (USP22) expression in NSCLC patient tissues was determined by RT-qPCR and Western blot. A xenograft model validated mogrol\'s effects on tumor growth. Bioinformatics identified four ubiquitin-specific proteases, including USP22, in NSCLC. Kaplan-Meier analysis confirmed USP22\'s value in lung cancer survival. Human Protein Atlas (HPA) database analysis indicated higher USP22 expression in lung cancer tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis implicated ERK1/2 in NSCLC progression, and molecular docking showed stability between mogrol and ERK1/2. Further in vivo and in vitro experiments have demonstrated that mogrol enhances the inhibitory effect of radiation on NSCLC cell viability and clonogenic capacity. Cell viability and clonogenic capacity are reduced by >50%, and an increase in cellular apoptosis is observed, with apoptotic levels reaching 10%. USP22 expression was significantly elevated in NSCLC tissues, particularly in radiotherapy-resistant patients. Mogrol downregulated USP22 expression by inhibiting the ERK/CREB pathway, lowering COX2 expression. Mogrol also enhanced radiation\'s inhibition of tumor growth in mice. Mogrol enhances NSCLC radiosensitivity by downregulating USP22 via the ERK/CREB pathway, leading to reduced COX2 expression.NEW & NOTEWORTHY Mogrol enhances non-small cell lung cancer (NSCLC) cell sensitivity to radiotherapy by downregulating USP22 through the ERK/CREB pathway, reducing COX2 expression. These findings highlight mogrol\'s potential as an adjunct to improve NSCLC radiotherapy and open avenues for further research and clinical applications.
摘要：
目的：使用各种方法，包括分析，研究Mogrol对NSCLC放射敏感性和潜在机制的影响，生物信息学，和异种移植模型。
方法：CCK-8，克隆，流式细胞术,TUNEL,和Western印迹分析评估了Mogrol和辐射对NSCLC活力和凋亡的影响。使用RT-qPCR和Western印迹测定NSCLC患者组织中的USP22表达。异种移植模型验证了Mogrol对肿瘤生长的影响。
结果：生物信息学鉴定了四种泛素特异性蛋白酶，包括USP22，在NSCLC中。Kaplan-Meier分析证实USP22在肺癌生存中的价值。HPA数据库显示肺癌组织中更高的USP22表达。GO和KEGG分析提示ERK1/2在NSCLC进展中，和分子对接显示Mogrol和ERK1/2之间的稳定性。进一步的体内和体外实验表明，Mogrol增强了辐射对NSCLC细胞活力和克隆形成能力的抑制作用。细胞活力和克隆形成能力降低50%以上，观察到细胞凋亡的增加，凋亡水平达到10%。USP22在NSCLC组织中表达显著升高，尤其是对放疗耐药的患者。Mogrol通过抑制ERK/CREB通路下调USP22表达，降低COX2表达。Mogrol还增强了辐射对小鼠肿瘤生长的抑制作用。
结论：Mogrol通过ERK/CREB通路下调USP22来增强NSCLC的放射敏感性，导致COX2表达降低。
方法：CCK-8，克隆，流式细胞术,TUNEL,和Western印迹分析评估了Mogrol和辐射对NSCLC活力和凋亡的影响。使用RT-qPCR和Western印迹测定NSCLC患者组织中的USP22表达。异种移植模型验证了Mogrol对肿瘤生长的影响。
结果：生物信息学鉴定了四种泛素特异性蛋白酶，包括USP22，在NSCLC中。Kaplan-Meier分析证实USP22在肺癌生存中的价值。HPA数据库显示肺癌组织中更高的USP22表达。GO和KEGG分析提示ERK1/2在NSCLC进展中，和分子对接显示Mogrol和ERK1/2之间的稳定性。进一步的体内和体外实验表明，Mogrol增强了辐射对NSCLC细胞活力和克隆形成能力的抑制作用。细胞活力和克隆形成能力降低50%以上，观察到细胞凋亡的增加，凋亡水平达到10%。USP22在NSCLC组织中表达显著升高，尤其是对放疗耐药的患者。Mogrol通过抑制ERK/CREB通路下调USP22表达，降低COX2表达。Mogrol还增强了辐射对小鼠肿瘤生长的抑制作用。
结论：Mogrol通过ERK/CREB通路下调USP22来增强NSCLC的放射敏感性，导致COX2表达降低。
