Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Sanguisorba officinalis L. (SOL), a traditional Chinese herbal medicine called Diyu, has been shown to have potent antitumor effects. However, the role of SOL in suppressing NSCLC remains unknown.Methods: Network...

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Main Authors: Hong Li, Jing Lin, Fei Yang, Junzhu Deng, Jia Lai, Jing Zeng, Wenjun Zou, Nan Jiang, Qianqian Huang, Hua Li, Jian Liu, Mao Li, Zhirong Zhong, Jianming Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1054803/full
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author Hong Li
Hong Li
Jing Lin
Fei Yang
Junzhu Deng
Jia Lai
Jing Zeng
Wenjun Zou
Nan Jiang
Nan Jiang
Qianqian Huang
Qianqian Huang
Hua Li
Jian Liu
Mao Li
Zhirong Zhong
Jianming Wu
Jianming Wu
Jianming Wu
author_facet Hong Li
Hong Li
Jing Lin
Fei Yang
Junzhu Deng
Jia Lai
Jing Zeng
Wenjun Zou
Nan Jiang
Nan Jiang
Qianqian Huang
Qianqian Huang
Hua Li
Jian Liu
Mao Li
Zhirong Zhong
Jianming Wu
Jianming Wu
Jianming Wu
author_sort Hong Li
collection DOAJ
description Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Sanguisorba officinalis L. (SOL), a traditional Chinese herbal medicine called Diyu, has been shown to have potent antitumor effects. However, the role of SOL in suppressing NSCLC remains unknown.Methods: Network pharmacology was employed for acquiring the potential targets and mechanisms of SOL in NSCLC. Based on the predictions of network pharmacology, we used CCK8 and EdU assays to investigate cell proliferation, flow cytometry to investigate apoptosis, wound healing assay to investigate cell migration, and transwell assay to investigate cell invasion in vitro. Western blot was employed for detecting the potential proteins, including signaling pathways and apoptosis. The A549-bearing athymic nude mice were employed to verify the effect on cell proliferation and apoptosis in vivo.Results: SOL significantly inhibited the proliferation, migration and invasion of NSCLC cells in a dose-dependent manner. Flow cytometry showed that the apoptotic ratio and ROS level of NSCLC cells increased significantly with increasing concentrations. AKT and the PI3K-AKT signaling pathway were analyzed as the most relevant target and pathway via network pharmacology predictions. Western blotting revealed that the expression levels of p-PI3K, p-AKT, and p-mTOR in NSCLC cells treated with SOL were significantly downregulated, while cleaved PARP-1 and caspase-3 were upregulated in a dose-dependent manner. The results in the mouse xenograft model were consistent with those in NSCLC cell lines.Conclusion: SOL downregulated the PI3K/AKT/mTOR signaling pathway to suppress NSCLC.
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spelling doaj.art-98c4261dbe644b3bb05ba6d4721e6ae52022-12-22T02:53:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10548031054803Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigationHong Li0Hong Li1Jing Lin2Fei Yang3Junzhu Deng4Jia Lai5Jing Zeng6Wenjun Zou7Nan Jiang8Nan Jiang9Qianqian Huang10Qianqian Huang11Hua Li12Jian Liu13Mao Li14Zhirong Zhong15Jianming Wu16Jianming Wu17Jianming Wu18School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Basic Medical University, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaThe Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Institute of Cardiovascular Research, Luzhou, ChinaBackground: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Sanguisorba officinalis L. (SOL), a traditional Chinese herbal medicine called Diyu, has been shown to have potent antitumor effects. However, the role of SOL in suppressing NSCLC remains unknown.Methods: Network pharmacology was employed for acquiring the potential targets and mechanisms of SOL in NSCLC. Based on the predictions of network pharmacology, we used CCK8 and EdU assays to investigate cell proliferation, flow cytometry to investigate apoptosis, wound healing assay to investigate cell migration, and transwell assay to investigate cell invasion in vitro. Western blot was employed for detecting the potential proteins, including signaling pathways and apoptosis. The A549-bearing athymic nude mice were employed to verify the effect on cell proliferation and apoptosis in vivo.Results: SOL significantly inhibited the proliferation, migration and invasion of NSCLC cells in a dose-dependent manner. Flow cytometry showed that the apoptotic ratio and ROS level of NSCLC cells increased significantly with increasing concentrations. AKT and the PI3K-AKT signaling pathway were analyzed as the most relevant target and pathway via network pharmacology predictions. Western blotting revealed that the expression levels of p-PI3K, p-AKT, and p-mTOR in NSCLC cells treated with SOL were significantly downregulated, while cleaved PARP-1 and caspase-3 were upregulated in a dose-dependent manner. The results in the mouse xenograft model were consistent with those in NSCLC cell lines.Conclusion: SOL downregulated the PI3K/AKT/mTOR signaling pathway to suppress NSCLC.https://www.frontiersin.org/articles/10.3389/fphar.2022.1054803/fullSanguisorba officinalis L.non-small cell lung cancernetwork pharmacologyPI3K/AKT/mTORROS
spellingShingle Hong Li
Hong Li
Jing Lin
Fei Yang
Junzhu Deng
Jia Lai
Jing Zeng
Wenjun Zou
Nan Jiang
Nan Jiang
Qianqian Huang
Qianqian Huang
Hua Li
Jian Liu
Mao Li
Zhirong Zhong
Jianming Wu
Jianming Wu
Jianming Wu
Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation
Frontiers in Pharmacology
Sanguisorba officinalis L.
non-small cell lung cancer
network pharmacology
PI3K/AKT/mTOR
ROS
title Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation
title_full Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation
title_fullStr Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation
title_full_unstemmed Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation
title_short Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation
title_sort sanguisorba officinalis l suppresses non small cell lung cancer via downregulating the pi3k akt mtor signaling pathway based on network pharmacology and experimental investigation
topic Sanguisorba officinalis L.
non-small cell lung cancer
network pharmacology
PI3K/AKT/mTOR
ROS
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1054803/full
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