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泽漆汤通过调控PI3K/Akt/p53信号通路抑制非小细胞肺癌的生长和转移。

Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway.

作者信息

Zhang Jingtao, Zhuang Zifan, Guo Minghao, Wu Kai, Yang Qingfeng, Min Xin, Cui Wenqiang, Xu Fei

机构信息

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.

College of First Clinical Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.

出版信息

J Tradit Complement Med. 2023 Mar 20;13(5):417-429. doi: 10.1016/j.jtcme.2023.03.008. eCollection 2023 Sep.

DOI:10.1016/j.jtcme.2023.03.008
PMID:37693094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10491987/
Abstract

BACKGROUND

The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation.

METHODS

Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments.

RESULTS

In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2.

CONCLUSIONS

ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.

摘要

背景

泽漆汤（ZQD）是中国常用于治疗肺癌的传统中药方剂。本研究旨在基于网络药理学并结合实验验证，评估泽漆汤治疗非小细胞肺癌（NSCLC）的有效成分和分子机制。

方法

进行网络药理学、生物信息学和分子对接分析，以探索泽漆汤治疗NSCLC的机制，并通过动物实验进一步证实。

结果

共鉴定出泽漆汤的117种生物活性成分和499种靶蛋白。网络药理学揭示了7种核心活性成分和74种核心靶蛋白。京都基因与基因组百科全书（KEGG）富集分析表明，PI3K/Akt和p53信号通路可能在NSCLC治疗中起关键作用。分子对接分析显示，7种关键生物活性成分与PI3K、Akt和p53结合。动物实验结果证实，泽漆汤治疗可促进细胞凋亡和细胞周期阻滞，从而抑制NSCLC的生长和转移。此外，泽漆汤治疗导致p53和Bax显著增加，而p-PI3K（Tyr317）、p-Akt（Ser473）、VEGFA、CD31、MMP2、MMP9、Bcl2和CDK2明显减少。

结论

泽漆汤通过PI3K/Akt/p53信号通路抑制C57BL/6J小鼠NSCLC皮下肿瘤的生长和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/30c9a2e643f0/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/b0102251a12c/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/03b64efda334/gr1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/d14c4378945e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/d8e238972ece/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/da2ef83edee2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/f25afee497f6/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/30c9a2e643f0/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/b0102251a12c/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/03b64efda334/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/9f6b9c0e5a7b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/d14c4378945e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/d8e238972ece/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/da2ef83edee2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/f25afee497f6/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102c/10491987/30c9a2e643f0/gr7.jpg

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