通过生物信息学和分子对接解码姜黄素治疗非小细胞肺癌的潜在靶点和药理机制。

IF 1.9 4区 医学 Q2 BIOLOGY
Jie Li, Zhen Zhang, Junchang Zhao, Shilin Liu, Chenghong Feng, Hong Deng, Dongwen Liu, Jing Zeng, Qin Yu, Dan Zhou, Milin Zhu, Yantao Liu
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引用次数: 0

摘要

新的证据表明,姜黄素对非小细胞肺癌(NSCLC)有抑制作用,其作用靶点和机制需要进一步探索。本研究旨在通过网络药理学、生物信息学和实验验证,探索姜黄素对NSCLC的潜在靶点和作用机制,从而为临床前和临床研究中姜黄素联合治疗NSCLC提供更多启示。根据HIT2.0、STD、CTD和DisGeNET预测了姜黄素抗NSCLC的靶点,并通过蛋白相互作用网络构建(PPI)、基因本体(GO)、京都基因组百科全书(KEGG)和分子对接分析了核心靶点。实时定量 PCR 检测了 A549 细胞、NCI-H460 和姜黄素处理组样本的基因表达水平。通过筛选公共数据库,共收集到姜黄素与 NSCLC 之间的 67 个共同靶点。GO和KEGG分析表明,姜黄素治疗NSCLC主要涉及癌症相关通路,如PI3K-AKT信号通路、Foxo信号通路、microRNAs、MAPK信号通路、HIF-1信号通路等。通过PPI网络确定的靶点中,CASP3、CTNNB1、JUN、IL6、MAPK3、HIF1A、STAT3、AKT1、TP53、CCND1、VEGFA和EGFR的靶点度最高。体外实验结果表明,姜黄素治疗NSCLC可下调CCND1、CASP3、HIF1A、IL-6、MAPK3、STAT3、AKT1和TP53的基因表达。我们的研究结果表明,姜黄素能抑制多种信号通路并与多种基因靶点相互作用,是治疗 NSCLC 的潜在候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Decoding potential targets and pharmacologic mechanisms of curcumin in treating non-small cell lung carcinoma via bioinformatics and molecular docking.

Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets.

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来源期刊
CiteScore
4.00
自引率
0.00%
发文量
129
审稿时长
2 months
期刊介绍: The Brazilian Journal of Medical and Biological Research, founded by Michel Jamra, is edited and published monthly by the Associação Brasileira de Divulgação Científica (ABDC), a federation of Brazilian scientific societies: - Sociedade Brasileira de Biofísica (SBBf) - Sociedade Brasileira de Farmacologia e Terapêutica Experimental (SBFTE) - Sociedade Brasileira de Fisiologia (SBFis) - Sociedade Brasileira de Imunologia (SBI) - Sociedade Brasileira de Investigação Clínica (SBIC) - Sociedade Brasileira de Neurociências e Comportamento (SBNeC).
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