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作 者:桑舒柳 丁蓉珍 姜靖洁 龚亚斌[1] Shu-Liu Sang;Rong-Zhen Ding;Jing-Jie Jiang;Ya-Bin Gong(Department of Oncology,Yue Yang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai,200437)
机构地区:[1]上海中医药大学附属岳阳中西医结合医院肿瘤科,上海200437
出 处:《TMR经典中医研究》2022年第4期19-31,共13页Classical Chinese Medicine Research
基 金:国家自然基金(NO.82074339);上海市自然基金(20ZR1459400)。
摘 要:目的:通过网络药理学筛选出鸦胆子治疗非小细胞肺癌的潜在靶点和相关通路探讨其作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP),并结合相关文献,筛选鸦胆子主要活性成分和可能的作用靶点;通过人类基因数据库(GeneCards)和DisGeNET数据库收集NSCLC相关靶点;采用Cytoscape 3.7.2软件构建活性成分-NSCLC靶点网络,并运用STRING数据库构建蛋白相互作用网络,利用Metascape数据库进行GO和KEGG的通路分析,在GEPA数据库筛选和肺腺癌患者生存相关的核心靶点。结果:共筛选出鸦胆子活性成分16个,它们共作用于230个靶点,最后筛选出与肺腺癌患者生存相关的核心靶点共14个。我们推测鸦胆子中的木犀草素、鸦胆亭和鸦胆醇共同靶向CDK1和PTGS2,主要作用于VEGF信号通路发挥治疗非小细胞肺癌的作用。结论:我们应用网络药理学方法研究了鸦胆子治疗NSCLC的分子起效机制,发现其拥有的多种活性成分可以通过不同途径有效地作用到多个关键致病靶点上,本研究结果将为鸦胆子的进一步实验研究和临床应用提供了理论依据。Objective:To use network pharmacology to explore molecular mechanisms associated with the Chinese medicinal herb,Brucea javanica,in the treatment of nonsmall cell lung cancer(NSCLC).Methods:The main active ingredients of B.javanica were screened using a combination of literature mining and the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform(TCMSP).Disease targets were identified through the human GeneCards and DisGeNET databases while Cytoscape(ver.3.7.2)was used to construct an active ingredient-disease target network.The following databases were used for network construction:STRING for a protein interaction network,Metascape for GO and KEGG pathway analysis,and GEPA for screening core targets associated with survival in lung adenocarcinoma.Results:Sixteen active ingredients from B.javanica were screened and were found to act on 230 targets;among these,14 were associated with survival in lung adenocarcinoma patients.As luteolin,bruceantin,and bruceantinol were the main bioactives in B.javanica that could act on key targets such as CDK1,PTGS2,and through the VEGF signaling pathway,we predict that they may be useful in the treatment of NSCLC.Conclusion:We used network pharmacology to predict potential molecular mechanisms involved in the treatment of NSCLC using B.javanica bioactives.These results will help lay the foundation for further experimental studies and clinical applications of this herb.
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