Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma

Objective: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor...

Full description

Bibliographic Details
Main Authors: Bin Xie PhD, Xiong Xie MS, Bin Rao MS, Shengzhang Liu MS, Hongning Liu PhD
Format: Article
Language:English
Published: SAGE Publishing 2018-06-01
Series:Integrative Cancer Therapies
Online Access:https://doi.org/10.1177/1534735417694953
_version_ 1819031606355034112
author Bin Xie PhD
Xiong Xie MS
Bin Rao MS
Shengzhang Liu MS
Hongning Liu PhD
author_facet Bin Xie PhD
Xiong Xie MS
Bin Rao MS
Shengzhang Liu MS
Hongning Liu PhD
author_sort Bin Xie PhD
collection DOAJ
description Objective: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor activity of QD in Lewis lung carcinomas (LLC) in vivo and in vitro, and to elucidate the underlying mechanisms. Methods: The LLC cells were used to assess the antitumor activity of QD by Cell Counting Kit-8 assay in vitro. In vivo, mice were randomly assigned to 5 groups (n = 10/group): the model control (MC) group was intragastrically administered physiological saline (0.9% NaCl) twice daily from day 2 after tumor implantation for 2 weeks. The QD groups were intragastrically administered QD twice daily from 2 weeks before to 2 weeks after tumor implantation for 4 weeks. The mRNA levels were detected by quantitative polymerase chain reaction, the proteins expression was determined by immunohistochemistry or western blotting. Results: Compared with the model group, QD showed inhibition of proliferation of LLC cells and reductions in tumor weight and proliferating cell nuclear antigen protein expression. Furthermore, QD up-regulated p53 mRNA expression, and downregulated c-myc and Bcl-2 mRNA expression, while MMP-9, VEGF, and VEGFR protein expression was suppressed. Phosphorylated ERK1/2 levels were also reduced by QD in a dose-dependent manner. Conclusion: Our findings suggest that QD inhibited lung tumor growth and proliferation, by activation of tumor suppressor genes, inactivation of oncogenes, suppressing the potential for invasion and metastasis, and attenuating angiogenesis. The ERK/VEGF/MMPs signaling pathways may play an important role in QD-induced inhibition of malignant tumor cell proliferation.
first_indexed 2024-12-21T06:48:43Z
format Article
id doaj.art-bb497459353643cf92533a67e0d2d6ca
institution Directory Open Access Journal
issn 1534-7354
1552-695X
language English
last_indexed 2024-12-21T06:48:43Z
publishDate 2018-06-01
publisher SAGE Publishing
record_format Article
series Integrative Cancer Therapies
spelling doaj.art-bb497459353643cf92533a67e0d2d6ca2022-12-21T19:12:31ZengSAGE PublishingIntegrative Cancer Therapies1534-73541552-695X2018-06-011710.1177/1534735417694953Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung CarcinomaBin Xie PhD0Xiong Xie MS1Bin Rao MS2Shengzhang Liu MS3Hongning Liu PhD4Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaJiangxi University of Traditional Chinese Medicine, Nanchang, ChinaJiangxi University of Traditional Chinese Medicine, Nanchang, ChinaJiangxi University of Traditional Chinese Medicine, Nanchang, ChinaJiangxi University of Traditional Chinese Medicine, Nanchang, ChinaObjective: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor activity of QD in Lewis lung carcinomas (LLC) in vivo and in vitro, and to elucidate the underlying mechanisms. Methods: The LLC cells were used to assess the antitumor activity of QD by Cell Counting Kit-8 assay in vitro. In vivo, mice were randomly assigned to 5 groups (n = 10/group): the model control (MC) group was intragastrically administered physiological saline (0.9% NaCl) twice daily from day 2 after tumor implantation for 2 weeks. The QD groups were intragastrically administered QD twice daily from 2 weeks before to 2 weeks after tumor implantation for 4 weeks. The mRNA levels were detected by quantitative polymerase chain reaction, the proteins expression was determined by immunohistochemistry or western blotting. Results: Compared with the model group, QD showed inhibition of proliferation of LLC cells and reductions in tumor weight and proliferating cell nuclear antigen protein expression. Furthermore, QD up-regulated p53 mRNA expression, and downregulated c-myc and Bcl-2 mRNA expression, while MMP-9, VEGF, and VEGFR protein expression was suppressed. Phosphorylated ERK1/2 levels were also reduced by QD in a dose-dependent manner. Conclusion: Our findings suggest that QD inhibited lung tumor growth and proliferation, by activation of tumor suppressor genes, inactivation of oncogenes, suppressing the potential for invasion and metastasis, and attenuating angiogenesis. The ERK/VEGF/MMPs signaling pathways may play an important role in QD-induced inhibition of malignant tumor cell proliferation.https://doi.org/10.1177/1534735417694953
spellingShingle Bin Xie PhD
Xiong Xie MS
Bin Rao MS
Shengzhang Liu MS
Hongning Liu PhD
Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma
Integrative Cancer Therapies
title Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma
title_full Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma
title_fullStr Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma
title_full_unstemmed Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma
title_short Molecular Mechanisms Underlying the Inhibitory Effects of Qingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma
title_sort molecular mechanisms underlying the inhibitory effects of qingzaojiufei decoction on tumor growth in lewis lung carcinoma
url https://doi.org/10.1177/1534735417694953
work_keys_str_mv AT binxiephd molecularmechanismsunderlyingtheinhibitoryeffectsofqingzaojiufeidecoctionontumorgrowthinlewislungcarcinoma
AT xiongxiems molecularmechanismsunderlyingtheinhibitoryeffectsofqingzaojiufeidecoctionontumorgrowthinlewislungcarcinoma
AT binraoms molecularmechanismsunderlyingtheinhibitoryeffectsofqingzaojiufeidecoctionontumorgrowthinlewislungcarcinoma
AT shengzhangliums molecularmechanismsunderlyingtheinhibitoryeffectsofqingzaojiufeidecoctionontumorgrowthinlewislungcarcinoma
AT hongningliuphd molecularmechanismsunderlyingtheinhibitoryeffectsofqingzaojiufeidecoctionontumorgrowthinlewislungcarcinoma