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基于网络药理学的研究以探索益气固表丸治疗肺癌的机制。

Network pharmacology-based study to explore the mechanism of the Yiqi Gubiao pill in lung cancer treatment.

作者信息

Li Zheng, Xu Dan, Jing Jing, Li Fengsen

机构信息

Respiratory Department, The Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China.

National Clinical Research Base of Traditional Chinese Medicine in Xinjiang, Urumqi, Xinjiang 830000, P.R. China.

出版信息

Oncol Lett. 2021 Apr;21(4):321. doi: 10.3892/ol.2021.12583. Epub 2021 Feb 23.

Abstract

Lung cancer (LC) has been one of the most prevalent and fatal malignancies in the past 5 years. Yiqi Gubiao pills have a good clinical effect against LC. However, their complex composition limits proper understanding of their pharmacological mechanism. Therefore, the present study aimed to systemically explore the underlying mechanisms of Yiqi Gubiao pills in treatment of LC. The network pharmacology approach was employed to identify the active ingredients and LC targets associated with Yiqi Gubiao pills. Prediction of potential active ingredients and action targets was then conducted through protein-protein interaction (PPI), Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. experiments were then performed to further verify the mechanism of action of Yiqi Gubiao pills, revealing that the anti-LC effects were mediated by regulating the expression of IL6, TP53, albumin (ALB), MAPK3 and AKT1. In total, 102 active ingredients and 229 targets of Yiqi Gubiao pills were identified. The PPI network further revealed that AKT1, TP53, ALB, IL6 and MAPK3 were the top five hub genes associated with LC treatment. Targets of the Yiqi Gubiao pills were mainly enriched in the PI3K-Akt and Advanced glycation end products (AGE)-receptors for AGEs (RAGE) signaling pathways. Overall, network pharmacology deciphered the active ingredients and potential targets of the Yiqi Gubiao pills. Yiqi Gubiao pills partially inhibited the progression of LC by regulating the expression of hub genes (AKT1, TP53, ALB, IL6 and MAPK3) through the PI3K-Akt and AGE-RAGE signaling pathways. The findings of the present study may provide a theoretical basis for the clinical application of Yiqi Gubiao pills in LC treatment.

摘要

肺癌(LC)在过去5年中一直是最常见且致命的恶性肿瘤之一。益气固表丸对肺癌具有良好的临床疗效。然而,其成分复杂,限制了对其药理机制的深入理解。因此,本研究旨在系统探索益气固表丸治疗肺癌的潜在机制。采用网络药理学方法确定与益气固表丸相关的活性成分和肺癌靶点。然后通过蛋白质-蛋白质相互作用(PPI)、基因本体论和京都基因与基因组百科全书通路分析对潜在活性成分和作用靶点进行预测。随后进行实验进一步验证益气固表丸的作用机制,结果表明其抗肺癌作用是通过调节白细胞介素6(IL6)、TP53、白蛋白(ALB)、丝裂原活化蛋白激酶3(MAPK3)和蛋白激酶B(AKT1)的表达来介导的。共鉴定出益气固表丸的102种活性成分和229个靶点。PPI网络进一步显示,AKT1、TP53、ALB、IL6和MAPK3是与肺癌治疗相关的前五个核心基因。益气固表丸的靶点主要富集于磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)和晚期糖基化终末产物(AGE)-AGE受体(RAGE)信号通路。总体而言,网络药理学解析了益气固表丸的活性成分和潜在靶点。益气固表丸通过PI3K-Akt和AGE-RAGE信号通路调节核心基因(AKT1、TP53、ALB、IL6和MAPK3)的表达,部分抑制了肺癌的进展。本研究结果可为益气固表丸在肺癌治疗中的临床应用提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5a5/7933746/756ecef5db89/ol-21-04-12583-g00.jpg

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