Diterpenoid Tanshinone Attenuates the Metastasis of Non-small-cell Lung Cancer
(NSCLC) Cells by Inhibiting the Cavin-1-mediated ERK/Smad2 Signaling Pathway
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Published:2023-08
Issue:14
Volume:23
Page:1618-1625
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ISSN:1871-5206
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Container-title:Anti-Cancer Agents in Medicinal Chemistry
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language:en
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Short-container-title:ACAMC
Author:
Wang Lu1ORCID, Jiang Gangdan2, Li Xiaojuan3
Affiliation:
1. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang
Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, P.R. China 2. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang
Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, P.R. China; 3. Department of Scientific Research, The First Affiliated
Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, P.R. China
Abstract
Background:
Non-small cell lung cancer (NSCLC) is a common malignant cancer with high incidence and
mortality. In recent decade, despite the progress in the treatment and prevention of NSCLC, its prognosis still remains
poor. It is urgently needed to identify new potential mechanism and efficacious drugs for NSCLC patients.
Objective:
The objective of this study is to explore the potential therapeutic role of diterpenoid tanshinone (DT) against
non-small cell lung cancer (NSCLC) in vitro and elucidate the molecular mechanism involved in tumor metastasis.
Methods:
Human NSCLC lines (A549 and NCI-H1299) were transfected with pcDNA3.1-Cavin-1 plasmids and corresponding
controls. We tested the effects of DT on migration and invasion of lung cancer cells using transwell filters
coated with fibronectin and Matrigel. Next, Quantitative Real-Time PCR and western blot were used to determine the
transcriptional and protein levels of epithelial-mesenchymal transition (EMT) markers, transcription factors (Snail,
Slug), and matrix metalloproteinases.
Results:
As expected, Cavin-1 related to the enhanced ability of cell migration and invasion. DT not only inhibited the
migratory and invasive capacity of Cavin-1-transfected NSCLC cells but also significantly increased the expression of
ZEB1 and E-cadherin and decreased the level of N-cadherin, Vimentin, Snail, and Slug. Moreover, DT treatment obviously
alleviated Cavin-1 overexpression-induced high levels of MMP2, MMP7, and MMP9 at both the protein and
transcriptional levels. Furthermore, overexpressed Cavin-1 upregulated ERK and Smad2 signaling pathways in
NSCLC cells, which were also strongly weakened by DT administration.
Conclusion:
Our results suggested that DT effectively attenuates Cavin-1-mediated NSCLC metastasis via the
ERK/Smad2 signaling pathway.
Funder
National Natural Science Foundation of Zhejiang Province National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
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