Wang Luyao, Chen Huili, Deng Lili, Hu Mengling, Wang Ziqiang, Zhang Kai, Lian Chaoqun, Wang Xiaojing, Zhang Jing
Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Department of Genetics, School of Life Sciences, Bengbu Medical University, Bengbu, China.
Front Oncol. 2024 Oct 10;14:1449143. doi: 10.3389/fonc.2024.1449143. eCollection 2024.
Roburic acid (ROB) is a newly discovered tetracyclic triterpene acid extracted from oak galls, which has anti-inflammatory effects, but the mechanism of its anticancer effect is not clear. Our study focuses on exploring the potential mechanism of action of ROB in the treatment of lung cancer using a combination of network pharmacological prediction, molecular docking technique and experimental validation.
A network pharmacology approach was used to screen the protein targets of ROB and lung cancer, and PPI network analysis and enrichment analysis were performed on the intersecting genes. The tissue and organ distribution of the targets was also evaluated based on the BioGPS database. To ensure the reliability of the network pharmacology prediction results, we proceeded to use molecular docking technique to determine the relationship between drugs and targets. Finally, experiments with cell lines were performed to further reveal the potential mechanism of ROB for the treatment of lung cancer.
A total of 83 potential targets of ROB in lung cancer were collected and further screened by using Cytoscape software, and 7 targets of PTGS2, CYP19A1, PTGS1, AR, CYP17A1, PTGES and SRD5A1 were obtained as hub genes and 7 hub targets had good binding energy with ROB. GO and KEGG analysis showed that ROB treatment of lung cancer mainly involves Arachidonic acid metabolism, Notch signaling pathway, cancer pathway and PPAR signaling pathway. The results of experiments indicated that ROB may inhibit the proliferation and metastasis of lung cancer cells and activate the PPARγ signaling pathway, as well as induce cellular autophagy.
The results of this study comprehensively elucidated the potential targets and molecular mechanisms of ROB for the treatment of lung cancer, providing new ideas for further lung cancer therapy.
罗布酸（ROB）是一种新发现的从五倍子中提取的四环三萜酸，具有抗炎作用，但其抗癌作用机制尚不清楚。我们的研究聚焦于结合网络药理学预测、分子对接技术和实验验证来探索罗布酸治疗肺癌的潜在作用机制。
采用网络药理学方法筛选罗布酸和肺癌的蛋白质靶点，对交集基因进行蛋白质-蛋白质相互作用（PPI）网络分析和富集分析。还基于BioGPS数据库评估靶点的组织和器官分布。为确保网络药理学预测结果的可靠性，我们继续使用分子对接技术确定药物与靶点之间的关系。最后，进行细胞系实验以进一步揭示罗布酸治疗肺癌的潜在机制。
共收集到罗布酸在肺癌中的83个潜在靶点，并使用Cytoscape软件进一步筛选，得到环氧化酶-2（PTGS2）、细胞色素P450 19A1（CYP19A1）、环氧化酶-1（PTGS1）、雄激素受体（AR）、细胞色素P450 17A1（CYP17A1）、前列腺素E合成酶（PTGES）和5α-还原酶1（SRD5A1）这7个靶点作为枢纽基因，且这7个枢纽靶点与罗布酸具有良好的结合能。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，罗布酸治疗肺癌主要涉及花生四烯酸代谢、Notch信号通路、癌症通路和过氧化物酶体增殖物激活受体（PPAR）信号通路。实验结果表明，罗布酸可能抑制肺癌细胞的增殖和转移，激活PPARγ信号通路，并诱导细胞自噬。
本研究结果全面阐明了罗布酸治疗肺癌的潜在靶点和分子机制，为进一步的肺癌治疗提供了新思路。
