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

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 wit...

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Main Authors: Jingtao Zhang, Zifan Zhuang, Minghao Guo, Kai Wu, Qingfeng Yang, Xin Min, Wenqiang Cui, Fei Xu
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Journal of Traditional and Complementary Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2225411023000433
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author Jingtao Zhang
Zifan Zhuang
Minghao Guo
Kai Wu
Qingfeng Yang
Xin Min
Wenqiang Cui
Fei Xu
author_facet Jingtao Zhang
Zifan Zhuang
Minghao Guo
Kai Wu
Qingfeng Yang
Xin Min
Wenqiang Cui
Fei Xu
author_sort Jingtao Zhang
collection DOAJ
description 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.
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spelling doaj.art-585a2e7e14db44178d8b3eed645724ba2023-09-01T05:02:17ZengElsevierJournal of Traditional and Complementary Medicine2225-41102023-09-01135417429Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathwayJingtao Zhang0Zifan Zhuang1Minghao Guo2Kai Wu3Qingfeng Yang4Xin Min5Wenqiang Cui6Fei Xu7College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, ChinaCollege of First Clinical Medicine, Beijing University of Chinese Medicine, Beijing, 100029, ChinaDepartment of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, ChinaDepartment of Pathology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, ChinaDepartment of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, ChinaFirst Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, ChinaDepartment of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China; Corresponding author. Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, China.Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China; Corresponding author. Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, China.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.http://www.sciencedirect.com/science/article/pii/S2225411023000433Traditional Chinese medicineNSCLCAntitumorMechanismSignaling pathway
spellingShingle Jingtao Zhang
Zifan Zhuang
Minghao Guo
Kai Wu
Qingfeng Yang
Xin Min
Wenqiang Cui
Fei Xu
Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway
Journal of Traditional and Complementary Medicine
Traditional Chinese medicine
NSCLC
Antitumor
Mechanism
Signaling pathway
title Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway
title_full Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway
title_fullStr Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway
title_full_unstemmed Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway
title_short Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway
title_sort ze qi decoction inhibits non small cell lung cancer growth and metastasis by modulating the pi3k akt p53 signaling pathway
topic Traditional Chinese medicine
NSCLC
Antitumor
Mechanism
Signaling pathway
url http://www.sciencedirect.com/science/article/pii/S2225411023000433
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